System for producing a graft device with a three-dimensional covering

ABSTRACT

A system for producing a graft device for a patient may comprise: an imaging device configured to produce image data of a tubular conduit; and a processing unit configured to receive the image data from the imaging device. The processing unit may comprise an algorithm configured to process the image data, and produce a construction signal based on the image data. A material delivery device may be configured to receive the construction signal from the processor, and deliver material to produce a 3D covering based on the construction signal. The graft device may comprise the 3D covering positioned about the tubular conduit. Graft devices and methods of producing graft devices may also be provided.

CROSS-REFERENCE

This application claims the benefit of U.S. Provisional Application Ser.No. 62/348,318, filed Jun. 10, 2016, the contents of which areincorporated herein in their entirety.

BACKGROUND

Devices in the field of rapid prototyping, using 3D computer aideddesign (CAD) data, can be used to produce various three-dimensional (3D)structures. These devices use geometric data, either as 3D solid models,or 2D slices using a scanning device, to produce a scale model, aphysical part, or an assembly via either an additive or subtractivemanufacturing method.

In the field of tissue engineering, 3D printers are used to producescaffolds, which can be subsequently seeded with cells, cultured exvivo, and then implanted as tissue replacements. Another approach is 3Dbioprinting, which can be used to fabricate living tissue constructs byincorporating living cells into a scaffold created during thefabrication process.

Current 3D printed implants are not customized to conform to patientspecific anatomical geometries, resulting in various limitations. Thereis a need for improved graft devices, and other three-dimensionalimplantable structures, that provide long term efficacy and safety.

SUMMARY

For these and other reasons, there is a general need for systems,devices and methods that can provide enhanced implantable devices formammalian patients. Desirably, the systems, devices and methods mayimprove long term efficacy and minimize surgical and devicecomplications such as those caused by improper or inadequate productionof an implantable device.

Embodiments of the systems, devices and methods described herein can bedirected to systems, devices and methods for producing graft devices andother devices for implanting in mammalian patients, as well as to theimplantable devices themselves.

According to an aspect of the present disclosure, a system for producinga graft device for a patient may comprise an imaging device configuredto produce image data of a tubular conduit, and a processing unitconfigured to receive the image data from the imaging device. Theprocessing unit can comprise an algorithm, the algorithm configured toprocess the image data, and produce a construction signal based on theimage data. The system may comprise a material delivery deviceconfigured to receive the construction signal from the processor, anddeliver material to produce a 3D covering based on the constructionsignal. The graft device may comprise the 3D covering positioned aboutthe tubular conduit.

In some cases, the material delivery device may be configured to deliverthe 3D covering onto the tubular conduit. In some cases, the 3D coveringmay be configured to be positioned about the tubular conduit after beingproduced by the material delivery device. In some cases, the graftdevice may comprise a coronary artery bypass graft. In some cases, thegraft device may comprise a dialysis graft.

In some cases, the graft device may comprise an implant selected fromthe group consisting of: artery bypass graft; coronary artery bypassgraft; dialysis graft; peripheral arterial bypass graft; great vesselreplacement; great vessel bypass graft; esophageal graft; trachealgraft; bronchial graft; biliary duct graft; intestinal graft; organtransplant vascular connection graft; neuronal replacement implant;ligament graft; ligament replacement; tendon graft; tendon replacement;transplant organ coating; fallopian tube; urethra; ureter; cartilage;hip joint; shoulder joint; intervertebral disc; menisci; and anycombination thereof.

In some cases, the imaging device may comprise a device selected fromthe group consisting of: computerized tomography (CT) imager; opticalcoherence tomography (OCT) imager; magnetic resonance imaging (MRI); 3DScanner; Camera; Infrared Camera; Ultrasound imager; and any combinationthereof.

In some cases, the image data may comprise information related to thetubular conduit. In some cases, the image data may comprise informationrelated to a portion of the patient's anatomy. In some cases, the imagedata may comprise data collected when the tubular conduit is in-situ.The image data can comprise data collected after the tubular conduit isharvested from the patient. In some cases, the image data may comprisedata collected after the tubular conduit is harvested from the patient.In some cases, the image data may comprise data selected from the groupconsisting of: surface topography data; surface geometry data; peripherydata; length data; diameter data; thickness data such as wall thicknessdata; taper data; eccentricity data; relative position data; trajectorydata; speed of motion data; relative angle data; radiopacity data; bloodflow data; echographic data; spectroscopic data; and any combinationthereof.

In some cases, the image data may comprise at least one discrete featureof the tubular conduit. The at least one discrete feature can beidentified by the algorithm. The at least one discrete feature cancomprise a feature selected from the group consisting of: sidebranch;recess; projection; end; end portion; bend portion; lobe; bifurcation;trifurcation; a dilated portion; a swollen portion; valve; a taperedportion; a location of a surgical staple; an angled portion; a calcifiedtissue portion; an atheromatous tissue portion; a partially occludedportion; a fully occluded portion; and any combination thereof. The atleast one discrete feature can comprise a sidebranch. The image data caninclude sidebranch information selected from the group consisting of:location; diameter; taper angle; ligation device position; ligationdevice geometry; ligation device type; and any combination thereof.

In some cases, the image data may comprise information related to thecompliance of the tubular conduit. In some cases, the image data maycomprise information related to the shape of the tubular conduitchanging over time. The information related to the shape of the tubularconduit changing over time can comprise information related to the shapeof the tubular conduit changing over time prior to harvesting. Thetubular conduit can change shape due to a change in a parameter selectedfrom the group consisting of: blood pressure; respiration; patientmovement; and any combination thereof.

In some cases, the tubular conduit may comprise tissue selected from thegroup consisting of: cylindrical tissue; organ tissue; saphenous vein;vein; artery; urethra; intestine; esophagus; ureter; trachea; bronchi;duct; fallopian tube; and any combination thereof. In some cases, thetubular conduit may comprise tissue selected from the group consistingof: bone; ligament; tendon; and any combination thereof In some cases,the tubular conduit may comprise artificial material.

In some cases, the processing unit may comprise memory circuitry. Thememory circuitry can be configured to store information selected fromthe group consisting of: tissue type; type of the material; informationregarding the application of the graft device; information regarding useof one or more tools; compliance information; density information;strength information; modulus of elasticity information; elastic limitinformation; wall thickness information; shrinkage information of thematerial; cure time information of the material; spacing to a mandreland/or other target; minimum bend radius of the covering; maximumovality of the covering; and any combination thereof. The constructionsignal can be based on information stored in the memory circuitry. Insome cases, the processing unit may comprise at least one of amicroprocessor or a microcontroller.

In some cases, the algorithm may be configured to identify at least onediscrete feature of the tubular conduit. The at least one discretefeature of the tubular conduit identified by the algorithm can comprisea feature selected from the group consisting of: sidebranch; recess;projection; end; end portion; bend portion; lobe; bifurcation;trifurcation; a dilated portion; a swollen portion; valve; a taperedportion; a location of a surgical staple; an angled portion; a calcifiedtissue portion; an atheromatous tissue portion; a partially occludedportion; a fully occluded portion; and any combination thereof. The 3Dcovering can comprise at least one customized portion positionedrelative to the at least one discrete feature. The customized portioncan be positioned proximate the at least one discrete feature. Thealgorithm can be configured to identify at least two discrete featuresof the tubular conduit, and the 3D covering can comprise at least twocustomized portions. The customized portion can comprise adifferentiating property selected from the group consisting of:different thickness; different material; different porosity; differentpore size; different compliance in one or more directions; differentlevel of conformality; different texture; different alignment and/ororientation of the deposited material; different stiffness; differentfiber diameter; addition of a kink-resisting element; addition of anagent; and any combination thereof. The at least one discrete featurecan comprise a protrusion of the tubular conduit. The protrusion cancomprise a sidebranch. The 3D covering can comprise a customized portionincluding a void proximate the protrusion. The void can comprise a hole.The void can comprise a recess. The at least one customized portion cancomprise a portion selected from the group consisting of: a portioncomprising a change in deposition of the material such as tomechanically reinforce and/or provide a strain relief at a sidebranchlocation; a portion configured to constrain a sidebranch such as tominimize hemodynamic disruption in a lumen of the tubular conduit; andany combination thereof. The 3D covering can comprise a customizedportion including a fillet positioned proximate the at least onediscrete feature. The at least one discrete feature can comprise an endof the tubular conduit. The 3D covering can comprise a customizedportion including a taper located proximate the end of the tubularconduit. The at least one discrete feature can comprise a second end ofthe tubular conduit, and the 3D covering can comprise a secondcustomized portion including a second tapered positioned proximate thesecond end of the tubular conduit. The 3D covering can comprise acustomized portion including a reinforced portion located proximate theend of the tubular conduit. The 3D covering can comprise a customizedportion including an optimized anastomosis portion located proximate theend of the tubular conduit. The optimized anastomosis portion cancomprise an optimized shape. The optimized anastomosis portion cancomprise an optimized structure. The at least one discrete feature cancomprise tissue whose softness is above a threshold. The customizedportion can comprise a differentiating property selected from the groupconsisting of: different material; different compliance; differentthickness; different permeability; different porosity; differentanisotropy; and any combination thereof. The at least one discretefeature can comprise tissue whose flexibility is above a threshold. Thecustomized portion can comprise a differentiating property selected fromthe group consisting of: different material; different compliance;different thickness; different permeability; different porosity;different anisotropy; and any combination thereof. The at least onediscrete feature can comprise tissue whose shape changes over time. Thecustomized portion can comprise a differentiating property selected fromthe group consisting of: different material; different compliance;different thickness; different permeability; different porosity;different anisotropy; and any combination thereof. The 3D covering caninclude a customized portion including a reinforced portion. The atleast one discrete feature can comprise a thin-walled portion of thetubular conduit, and the customized portion can be located proximate thethin-walled portion. The 3D covering can include a customized portionincluding a strain relief. The at least one discrete feature cancomprise at least one of an end of the tubular conduit or a bend portionof the graft device, and the customized portion can be located proximatethe at least one discrete feature. The 3D covering can include acustomized portion including modified porosity. The at least onediscrete feature can comprise an anastomosis site and/or a segment ofhigh curvature of the graft device, and the customized portion can belocated proximate the at least one discrete feature. The 3D covering caninclude a customized portion including a modified compliance. Themodified compliance can comprise a modified radial compliance. Themodified compliance can comprise a modified axial compliance. The atleast one discrete feature can comprise an anastomosis site, a ligamentattachment site, a tendon attachment site and/or a site of segmentedcompliance, and the customized portion can be located proximate the atleast one discrete feature.

In some cases, the algorithm may be configured to create a 3D model ofthe tubular conduit based on the image data. The 3D model can comprise aspatial model. The algorithm can be configured to modify the 3D model ofthe tubular conduit. The image data can comprise multiple slices of a CTimage. In some cases, the algorithm may be configured to create a 3Dmodel of a proposed 3D cover.

In some cases, the algorithm may be configured to create a proposed 3Dmodel of the 3D covering, and to modify the proposed 3D model to createa final 3D model of the 3D covering. The algorithm can be configured tomodify the proposed 3D model based on at least one discrete feature ofthe tubular conduit. The algorithm can be configured to modify theproposed 3D model based on user input.

In some cases, the algorithm may be configured to create a 3D model ofat least one of the tubular conduit or the 3D covering based on boundaryconditions. The algorithm can be configured to optimize hemodynamicswithin the tubular conduit by performing a function selected from thegroup consisting of: reducing flow turbulence; controlling bendingradius; controlling lumen geometry; controlling a transition;controlling a taper; controlling a bend portion; controlling tortuosity;controlling wall shear; preventing buckling; optimizing wall shearstress; modifying an end portion to optimize an anastomotic connection;reducing geometric mismatch near an anastomotic connection; and anycombination thereof.

In some cases, the algorithm may be configured to convert informationfrom an imaging coordinate system to a material deposition coordinatesystem. The imaging coordinate system can comprise Cartesian coordinatesand the material deposition coordinate system can comprise acylindrical, spherical and/or curvilinear coordinate system.

In some cases, the material delivery device may comprise at least onenozzle, and the algorithm may be configured to create a pathway ofmotion for the at least one nozzle. The algorithm can create the pathwayof motion based on one or more off limits locations. The pathway ofmotion can avoid portions of the 3D covering that have already beencreated. The pathway of motion can avoid the tubular conduit. Thematerial delivery device can comprise a mandrel, and the pathway ofmotion can avoid the mandrel. The pathway of motion can minimizedissipation of heat to the tubular conduit. The pathway of motion canreduce multiple passes of delivery of material in neighboring regions ofthe tubular conduit within a time period.

In some cases, the algorithm may be configured to perform aself-diagnostic. The system can comprise at least one sensor configuredto produce a signal, and the self-diagnostic can be based on the signalfrom the at least one sensor. The sensor can comprise one or moresensors selected from the group consisting of: an optical sensor; alaser; a magnetic sensor; an electrical sensor; an energy sensor; apressure sensor; a force sensor; a strain gauge; a position sensor; aflow sensor; a sound sensor; an ultrasound sensor; a humidity sensor;and any combination thereof. The self-diagnostic can be configured toassess a parameter selected from the group consisting of: electricalconnection status; rotational speed; translational speed; nozzle status;material delivery status; temperature; chamber environment condition;energy delivered; home position; a distance between two components ofthe system; and any combination thereof.

In some cases, the algorithm may be configured to create theconstruction signal based on a property of the tubular conduit. Theconstruction signal can produce a 3D covering that provides mechanicalsupport to the tubular conduit. The construction signal can produce a 3Dcovering with varied properties along a length of the tubular conduit.

In some cases, the material delivery device may comprise at least onenozzle. The material delivery device can comprise at least two nozzles.In some cases, the material delivery device may comprise a 3D printer.In some cases, the material delivery device may be configured to deliverthe material using an additive printing process. In some cases, thematerial delivery device may be configured to deliver the material as aseries of layers.

In some cases, the material delivery device may comprise a deviceselected from the group consisting of: a 3D printer; a layer printingdevice; an electrospinning device; a melt-spinning device; amelt-electrospinning device; a misting assembly; a sprayer; anelectrosprayer; a fused deposition device; a selective laser sinteringdevice; a fiber dispenser; a wire dispenser; a thread dispenser; a resindeposition device, such as a UV-curable resin deposition device; astereolithography device; a phase separation device; a wet spinningdevice; a dip coating device; a lathe; a milling machine; a chemicaletching device; a plasma etching device; a negative mold-over device; aninjection molding device; and any combination thereof. The materialdelivery device can comprise two or more devices selected from the groupconsisting of: a 3D printer; a layer printing device; an electrospinningdevice; a melt-spinning device; a melt-electrospinning device; a mistingassembly; a sprayer; an electrosprayer; a fused deposition device; aselective laser sintering device; a fiber dispenser; a wire dispenser; athread dispenser; a resin deposition device, such as a UV-curable resindeposition device; a stereolithography device; a phase separationdevice; a wet spinning device; a dip coating device; a lathe; a millingmachine; a chemical etching device; a plasma etching device; a negativemold-over device; an injection molding device; and any combinationthereof.

In some cases, the material may comprise one or more materials selectedfrom the group consisting of: synthetic polymer; natural polymer;protein; metal; metal alloy; collagen; elastin; a glycosaminoglycan(e.g. heparin, heparan sulfate, chondroitin sulfate, dermatan sulfate,keratan sulfate, and/or hyaluronic acid); a proteoglycan (e.g. decorin,biglycan, testican, bikunin, fibromodulin, lumican, versican, perlecan,neurocan, aggrecan and/or brevican); an alginate; cellulose; gelatin;silk fibroin; fibrinogen; chitosan; an enzyme; fibronectin; glycerin;integrin; keratin; a vitamin; a carbohydrate; a monosaccharide; adisaccharide; a polysaccharide; a nucleoside; abductin; lignin; aglycolipid; a phospholipid; a sterol; shrilk; cobalt-chrome; nitinol;aluminum oxide; magnesium; iron; zinc; steel; titanium; vitalium;alacrite; platinum; gold; silver; copper; manganese; a polyester; apolyurethane; a polycarbonate; a polyether; a polysulfone; a polyamide;a polyetheramide; a polystyrene; a polybutadiene; a polyisoprene; apoly(methyl methacrylate); a polyanhydride; a polydimethylsiloxane; apolydioxanone; polyethylene; glycol; polyethylene terephthalate; apolyglycolide; a polyhydroxyalkanoate; polyimide;polytetrafluoroethylene; polyvinylidene fluoride; polyethylene;polypropylene; polyvinylfluoride; polyvinylchloride; polyacylonitrile;silicone; a ceramic; a bioceramic; a bioglass; a composite material; andany combination thereof.

In some cases, the 3D covering may comprise varied properties along itslength. The 3D covering can comprise at least one customized portion. Insome cases, the 3D covering may comprise at least a portion with athickness from about 10 micrometers (μm) to about 1 centimeter (cm). The3D covering can comprise at least a portion with a thickness from about50 μm to about 500 μm. The 3D covering can comprise at least a portionwith a thickness from about 200 μm to about 300 μm.

In some cases, the 3D covering may comprise at least a portion with abulk porosity less than about 99%. The 3D covering can comprise at leasta portion with a bulk porosity from about 1% to about 90%. The 3Dcovering can comprise at least a portion with a bulk porosity from about10% to about 80%. The 3D covering can comprise at least a portion with abulk porosity from about 30% to about 80%. The 3D covering can compriseat least a portion with a bulk porosity from about 50% to about 70%.

In some cases, the 3D covering may comprise a length from about 1millimeter (mm) to about 1 meter (m). The 3D covering can comprise alength from about 3 cm to about 50 cm. The 3D covering can comprise alength from about 20 cm to about 30 cm.

In some cases, the 3D covering may comprise at least a portion with acompliance under a physiologic load that is less than about 99%. The 3Dcovering can comprise at least a portion with a compliance under aphysiologic load that is from about 1% to about 50%. The 3D covering cancomprise at least a portion with a compliance under a physiologic loadthat may be from about 10% to about 25%.

In some cases, the 3D covering may comprise at least a portion with anultimate strength from about 0.1 megapascal (MPa) to about 500 MPa. The3D covering can comprise at least a portion with an ultimate strengthfrom about 0.5 MPa to about 100 MPa. The 3D covering can comprise atleast a portion with an ultimate strength from about 1 MPa to about 10MPa.

In some cases, the 3D covering may comprise at least a portion with abiodurability from about 1 hour to about 10 years. The 3D covering cancomprise at least a portion with a biodurability from about 48 hours toabout 2 years. The 3D covering can comprise at least a portion with abiodurability from about 3 months to about 6 months.

In some cases, the 3D covering may comprise a drug, and the 3D coveringcan be configured to release the drug for a duration from about 1 hourto about 10 years. The 3D covering can be configured to release the drugfor a duration from about 48 hours to about 2 years. The 3D covering canbe configured to release the drug for a duration from about 3 months toabout 6 months.

In some cases, the 3D covering may comprise at least a portion with amacropore size from about 10 μm to about 1000 μm. The 3D covering cancomprise at least a portion with a macropore size from about 20 μm toabout 200 μm. The 3D covering can comprise at least a portion with amacropore size from about 50 μm to about 100 μm.

In some cases, the 3D covering may comprise at least a portion with amacropore spacing from about 10 μm to about 1000 μm. The 3D covering cancomprise at least a portion with a macropore spacing from about 100 μmto about 500 μm. The 3D covering can comprise at least a portion with amacropore spacing from about 200 μm to about 400 μm.

In some cases, the 3D covering may comprise at least a portion with awater permeability of less than about 300 milliliter per centimetersquared per minute (ml/cm2/min). The 3D covering can comprise at least aportion with a water permeability from about 50 ml/cm2/min to about 200ml/cm2/min. The 3D covering can comprise at least a portion with a waterpermeability from about 100 ml/cm2/min to about 150 ml/cm2/min.

In some cases, the 3D covering may comprise a texture with from about0.25 nanometer (nm) to about 50 μm roughness value Ra. The 3D coveringcan comprise a texture with from about 0.2 μm to about 12.5 μm roughnessvalue Ra. The 3D covering can comprise a texture with from about 1.6 μmto about 6.3 μm roughness value Ra.

In some cases, the 3D covering may comprise a suture retention strengthup to about 1 kilogram-force (Kgf). The 3D covering can comprise asuture retention strength of from about 50 gram-force (gf) to about 500gf. The 3D covering can comprise a suture retention strength of between100 gf and 200 gf.

In some cases, the 3D covering may comprise at least a portion with akink radius of up to about 1 meter (m). The 3D covering can comprise atleast a portion with a kink radius of from about 5 mm to about 100 mm.The 3D covering can comprise at least a portion with a kink radius offrom about 10 mm to about 20 mm.

In some cases, the 3D covering may comprise fibers with a width and/ordiameter from about 10 μm to about 1 mm. The 3D covering can comprisefibers with a width and/or diameter from about 20 μm to about 500 μm.The 3D covering can comprise fibers with a width and/or diameter fromabout 50 μm to about 100 μm.

In some cases, at least a portion of the 3D covering may comprise agreater axial compliance than radial compliance. The at least a portionof the 3D covering can comprise a majority of fibers that arecircumferentially oriented.

In some cases, at least a portion of the 3D covering may comprise anaxial compliance that is relatively equal to its radial compliance. Theat least a portion of the 3D covering can comprise a majority of fibersthat are anisotropically oriented.

In some cases, the 3D covering may comprise a material selected from thegroup consisting of: fiber reinforced material; particle reinforcedmaterial; flake reinforced material; a multi-layered material; asegmented material; and any combination thereof.

In some cases, the system may comprise a user interface. The system canbe configured to display an image of the tubular conduit on the userinterface. The displayed image can be a 3D image. The system can beconfigured to allow a user to modify the displayed image. The system canbe configured to display an image of a proposed 3D covering. Thedisplayed image can be a 3D image. The system can be configured to allowa user to modify the displayed image. The user interface can comprise auser control comprising an electronic model modifying tool. The tool canbe configured to modify a model of the tubular conduit. The tool can beconfigured to modify a model of a proposed 3D covering. The tool cancomprise a property modifying function selected from the groupconsisting of: smooth; erase; spline; fillet, fill; insert a buildingblock; and any combination thereof. The tool can comprise a propertymodifying function including inserting a building block, the buildingblock comprising an electronic model selected from the group consistingof: anastomosis; dimple; reinforcing spline; and any combinationthereof. The tool can be configured to measure distance. Theconstruction signal can be based on information provided by a user ofthe system via the user interface.

In some cases, the material delivery device may comprise a modificationassembly configured to modify at least one of the 3D covering or thetubular conduit. The modification assembly can be configured to deliverenergy to at least one of the 3D covering or the tubular conduit. Theenergy can comprise heat and/or cooling. The modification assembly canbe configured to deliver a second material to at least one of the 3Dcovering or the tubular conduit. The second material can comprise amaterial selected from the group consisting of: solvent; drug; agent;and any combination thereof. The modification assembly can be configuredto deliver moisture to at least one of the 3D covering or the tubularconduit.

In some cases, the system may comprise a target onto which the materialis delivered. The target can comprise a mandrel configured to rotate.The material delivery device can be constructed and arranged to producethe target. The target can comprise a disposable component.

In some cases, the system may comprise a sterile barrier constructed andarranged to maintain sterility between the material delivery device andone or more other portions of the system.

According to another aspect of the present disclosure, a graft devicemay be produced by a system as described herein. The graft device maycomprise a tubular conduit and a 3D covering surrounding the tubularconduit, and the 3D covering may be produced by a material deliverydevice of the system. The material delivery device may produce the 3Dcovering based on image data of the tubular conduit. The tubular conduitcan comprise a discrete feature, and the 3D covering can comprise atleast one customized portion positioned relative to the discretefeature.

According to another aspect of the present disclosure, a method ofproducing a graft device uses a system as described herein. The methodmay comprise (1) producing image data of a tubular conduit, (2)receiving the image data of the tubular conduit and creating anelectronic model of the tubular conduit, (3) creating an electronicmodel of a 3D covering and (4) delivering material to produce a 3Dcovering. The method can comprise modifying the electronic model of thetubular conduit produced in (2). The system can comprise modifying theelectronic model of the 3D covering produced in (3). The method 3Dcovering produced in (4) can be produced by delivering the material ontothe tubular conduit (e.g. directly onto the tubular conduit). The methodcan comprise a (5) including placing the 3D covering about the tubularconduit.

The technology described herein, along with the attributes and attendantadvantages thereof, may best be appreciated and understood in view ofthe following detailed description taken in conjunction with theaccompanying drawings in which representative embodiments are describedby way of example.

INCORPORATION BY REFERENCE

All publications, patents, and patent applications herein areincorporated by reference to the same extent as if each individualpublication, patent, or patent application was specifically andindividually indicated to be incorporated by reference. To the extentpublications and patents or patent applications incorporated byreference contradict the disclosure contained in the specification, thespecification is intended to supersede or take precedence over any suchcontradictory material.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates a schematic view of a system for producing a graftdevice.

FIG. 1A illustrates a side sectional view of a graft device comprising acovering including multiple customized portions.

FIG. 1B illustrates a side sectional view of a graft device comprising acovering including a large proportion of isotropically oriented fibers.

FIG. 1C illustrates a side sectional view of a graft device comprising acovering including a large proportion of circumferentially orientedfibers.

FIG. 2 illustrates a flow chart of a method of producing a graft deviceusing the system of FIG. 1.

FIG. 3 illustrates a schematic view of a particular embodiment of thesystem of FIG. 1.

DETAILED DESCRIPTION

Reference will now be made in detail to the present embodiments of thetechnology, examples of which are illustrated in the accompanyingdrawings. The same reference numbers are used throughout the drawings torefer to the same or like parts.

It may be further understood that the words “comprising” (and any formof comprising, such as “comprise” and “comprises”), “having” (and anyform of having, such as “have” and “has”), “including” (and any form ofincluding, such as “includes” and “include”) or “containing” (and anyform of containing, such as “contains” and “contain”) when used herein,specify the presence of stated features, integers, steps, operations,elements, and/or components, but may not preclude the presence oraddition of one or more other features, integers, steps, operations,elements, components, and/or groups thereof.

As used herein, the term “about” may mean the referenced numericindication plus or minus 15% of that referenced numeric indication.

It may be understood that, although the terms first, second, third etc.may be used herein to describe various limitations, elements,components, regions, layers and/or sections, these limitations,elements, components, regions, layers and/or sections may not be limitedby these terms. These terms may only be used to distinguish onelimitation, element, component, region, layer or section from anotherlimitation, element, component, region, layer or section. Thus, a firstlimitation, element, component, region, layer or section discussed belowmay be termed a second limitation, element, component, region, layer orsection without departing from the teachings of the present application.

It may be further understood that when an element may be referred to asbeing “on”, “attached”, “connected” or “coupled” to another element, itcan be directly on or above, or connected or coupled to, the otherelement, or one or more intervening elements can be present. Incontrast, when an element may be referred to as being “directly on”,“directly attached”, “directly connected” or “directly coupled” toanother element, there may be no intervening elements present. Otherwords used to describe the relationship between elements may beinterpreted in a like fashion (e.g. “between” versus “directly between,”“adjacent” versus “directly adjacent,” etc.).

It may be further understood that when a first element may be referredto as being “in”, “on” and/or “within” a second element, the firstelement can be positioned: within an internal space of the secondelement, within a portion of the second element (e.g. within a wall ofthe second element); positioned on an external and/or internal surfaceof the second element; and any combination thereof.

As used herein, the term “proximate” may generally refer to locationsrelatively close to, on, in and/or within a referenced component orother location.

Spatially relative terms, such as “beneath,” “below,” “lower,” “above,”“upper” and the like may generally refer to an element and/or feature'srelationship to another element(s) and/or feature(s) as, for example,illustrated in the figures. It may be understood that the spatiallyrelative terms may be intended to encompass different orientations ofthe device in use and/or operation in addition to the orientationdepicted in the figures. For example, if the device in a figure may beturned over, elements described as “below” and/or “beneath” otherelements or features may then be oriented “above” the other elements orfeatures. The device can be otherwise oriented (e.g. rotated about 90degrees or at other orientations) and the spatially relative descriptorsused herein interpreted accordingly.

As described herein, “room pressure” may generally refer to a pressureof the environment surrounding the systems and devices as describedherein. Positive pressure may include pressure above room pressure orsimply a pressure that may be greater than another pressure, such as apositive differential pressure across a fluid pathway component such asa valve. Negative pressure may include pressure below room pressure or apressure that may be less than another pressure, such as a negativedifferential pressure across a fluid component pathway such as a valve.Negative pressure can include a vacuum but does not imply a pressurebelow a vacuum. As used herein, the term “vacuum” can be used to referto a full or partial vacuum, or any negative pressure as describedherein.

The term “diameter” may generally refer to a non-circular geometry andin some cases may be taken as the diameter of a hypothetical circleapproximating the geometry being described. For example, when describinga cross section, such as the cross section of a component, the term“diameter” may be taken to represent the diameter of a hypotheticalcircle with the same cross sectional area as the cross section of thecomponent being described.

The terms “major axis” and “minor axis” of a component may generallyrefer to the length and diameter, respectively, of the smallest volumehypothetical cylinder which can completely surround the component.

The terms “reduce”, “reducing”, “reduction” and the like, may generallyrefer to a reduction in a quantity, including a reduction to zero.Reducing the likelihood of an occurrence may include prevention of theoccurrence.

The term “and/or” where used herein may be taken as specific disclosureof each of the two specified features or components with or without theother. For example “A and/or B” may be to be taken as specificdisclosure of each of (i) A, (ii) B and (iii) A and B, just as if eachmay be set out individually herein.

The term “biodurability” may in some cases generally refer to apreservation of one or more physical properties, one or more mechanicalproperties, one or more chemical properties, or any combination thereofduring an exposure to a biological environment or a biologically similarenvironment over a period of time. In some cases, a period of time maycomprise an extended period of time. In some cases, a period of time maycomprise about 1 month, about 6 months, about 1 year, about 2 years,about 5 years, about 10 years or more. A biological environment maycomprise a surface of a subject. A biological environment may comprisean internal surface or internal volume of a subject. A biologicallysimilar environment may comprise an artificial setting such as a mediasolution or incubator environment that simulates a biologicalenvironment.

The term “bulk porosity” may in some cases generally refer to a bulkporosity of a material or structure, such as a processed material orstructure. A bulk porosity may be equivalent to 1−W/(μV) where W equalsa weight of a material or structure, μ may be the weight per unit volumeof a material or structure prior to a processing, and V may be thevolume of the material or structure, such as the processed material orstructure.

The term “macropore” may in some cases generally refer to a lumenthrough a wall of a structure (such as a matrix) having a crosssectional area of at least about 3E-4 millimeters squared (mm²), atleast about 3E-3 mm², or at least about 1E-2 mm².

The term “kink radius” may in some cases generally refer to an innerradius of a structure (such as a tube) measured when the structure maybe bent to a limit before buckling may occur.

It is appreciated that certain features of the invention, which are, forclarity, described in the context of separate embodiments, may also beprovided in combination in a single embodiment. Conversely, variousfeatures of the invention which are, for brevity, described in thecontext of a single embodiment, may also be provided separately or inany suitable sub-combination. For example, it may be appreciated thatall features set out in any of the claims (whether independent ordependent) can be combined in any given way.

Provided herein are medical devices for implantation in a mammalianpatient, as well as systems, devices and methods for producing thesemedical devices. The medical devices can comprise graft devices that areimplanted to carry fluids (e.g. blood or other body fluid) from a firstanatomical location to a second anatomical location of the patient. Thegraft devices may include a conduit or other implantable structure(“conduit” herein), such as a harvested blood vessel segment or othertubular conduit, other harvested tissue and/or an artificial conduit,and a three-dimensional (3D) covering that surrounds the conduit. Thesystems can comprise a material delivery device configured to producethe 3D covering (e.g. directly onto the conduit or fabricated separatelyfor subsequent placement about the conduit). The systems describedherein can include a processing unit that receives image data related tothe patient's anatomy, such as image data related to an organ or othertissue. In some cases, the image data may be related to a tubularconduit or other tissue of a patient (e.g. data from one or more imagesof an in-vivo tubular tissue conduit and/or from images of an alreadyharvested tubular tissue conduit). The processing unit can produce aconstruction signal based on the image data, the construction signalused by the material delivery device to produce the 3D covering.

Referring now to FIG. 1, a system for creating an implantable device fora patient is illustrated. System 10 may comprise processing unit 200 anda material delivery device (MDD) 300. System 10 may be constructed andarranged to produce an implantable device, such as graft device 100which may comprise a three-dimensional (3D) covering, covering 110,which can be positioned about an implantable structure, conduit 120,such as a tubular conduit or other implantable structure. System 10 cancomprise an imaging device, such as imager 400 shown, which producesimage data 410. Image data 410 can represent information related toconduit 120 and/or a portion of a patient's anatomy (e.g. a portion ofthe patient's cardiovascular system).

Processing unit 200 may be configured to receive image data 410 fromimager 400. Imager 400 can comprise an imaging device selected from thegroup consisting of: CT imager; OCT imager; MRI; 3D Scanner; camera;infrared camera; ultrasound imager; laser-scanning device; and anycombination thereof. Imager 400 can produce image data 410 (e.g. imagedata of conduit 120 and/or any portion of the patient's anatomy), andprocessing unit 200 can receive the image data 410 from imager 400.

Image data 410 can be collected from an in-situ conduit 120 (e.g. avein, artery or other blood vessel, prior to being harvested) and/orafter conduit 120 has been harvested from the patient. In some cases,image data 410 may comprise data collected both prior to and after aconduit 120 has been harvested from the patient. Image data 410 cancomprise various geometric and other information of conduit 120, such asdata selected from the group consisting of: surface topography data;surface geometry data; periphery data; length data; diameter data;thickness data such as wall thickness data; taper data; eccentricitydata; relative position data; trajectory data; speed of motion data;relative angle data; radiopacity data; blood flow data; echographicdata; spectroscopic data; and any combination thereof. Image data 410can comprise data related to one or more abnormalities or otherparticular, relatively discrete, features of conduit 120, feature 121.In the embodiment shown in FIG. 1, conduit 120 may comprise feature 121comprising a sidebranch. In some cases, feature 121 of conduit 120 cancomprise one or more discrete features selected from the groupconsisting of: sidebranch; recess; projection; end; end portion; bendportion (e.g. a region of bending); lobe; bifurcation; trifurcation; adilated portion; a swollen portion; valve; a tapered portion; a locationof a surgical staple; an angled portion; a calcified tissue portion; anatheromatous tissue portion; a partially occluded portion; a fullyoccluded portion; and any combination thereof. In some cases, image data410 can comprise sidebranch data selected from the group consisting of:location; diameter; taper angle; and any combination thereof. One ormore sidebranches of conduit 120 may include a ligation device (e.g.suture or a ligation clip placed after harvest of conduit 120), andimage data 410 can include information related to the position of theligation device, ligation device geometry and/or ligation device type.

Processing unit 200 can comprise one or more algorithms, algorithm 250.Processing unit 200 can be configured to receive, process (e.g.mathematically process), store and/or transmit data. Processing unit 200can be configured to receive image data 410 from imaging device 400, andalgorithm 250 can be configured to process the received image data 410to produce a construction signal, construction signal 201. Constructionsignal 201 can comprise geometry and other construction information usedby material delivery device (MDD) 300 to produce covering 110.Construction signal 201 can be based on one or more properties ofconduit 120 (e.g. as determined by algorithm 250). Construction signal201 can be configured to produce a covering 110 that has variedproperties along the length of covering 110, such as to providemechanical support for conduit 120 at one or more particular locations.MDD 300 can receive construction signal 201 from processing unit 200,and deliver one or more materials, material 350, to produce covering 110based on construction signal 201. In some cases, MDD 300 may delivermaterial 350 directly onto conduit 120 while producing covering 110. Insome cases, covering 110 may be positioned about conduit 120 aftercovering 110 is produced by MDD 300.

Conduit 120 can comprise living tissue (including previously harvestedtissue), such as one or more segments of tissue selected from the groupconsisting of: cylindrical tissue; organ tissue; saphenous vein; vein;artery; urethra; intestine; esophagus; ureter; trachea; bronchi; duct;fallopian tube; and any combination thereof. In some cases, conduit 120can comprise an artificial material (e.g. a plastic or other non-tissuetube or other structure). In some cases, conduit 120 may comprise afirst length of tissue that may be subsequently shortened (e.g. one ormore ends cut off) during the creation of graft device 100. In somecases, conduit 120 may comprise a single lumen structure of tissue. Insome cases, conduit 120 may comprise a tubular structure including atleast a bifurcation or trifurcation of lumens. In some cases, conduit120 may comprise bone, ligament and/or tendon tissue. Conduit 120 cancomprise one or more discrete features 121 as described above, such as adiscrete feature 121 that may be identified by algorithm 250 (e.g.identified by analyzing image data 410).

Graft device 100 can be used as an arterial bypass graft, such as to beused as a coronary artery bypass graft. In some cases, graft device 100may be configured for use as a dialysis graft. In some cases, graftdevice 100 may comprise one or more graft devices configured to be usedas graft selected from the group consisting of: artery bypass graft;coronary artery bypass graft; dialysis graft; peripheral arterial bypassgraft; great vessel replacement; great vessel bypass graft; esophagealgraft; tracheal graft; bronchial graft; biliary duct graft; intestinalgraft; organ transplant vascular connection graft; neuronal replacementimplant; ligament graft; ligament replacement; tendon graft; tendonreplacement; transplant organ coating; fallopian tube; urethra; ureter;cartilage; hip joint; shoulder joint; intervertebral disc; menisci; andany combination thereof.

As described herein, covering 110 may include varied properties alongits length, such as when covering 110 comprises one or more customizedportions 111. In some cases, one or more customized portions 111 may beprovided based on image data 410 (e.g. as determined by algorithm 250).In some cases, one or more customized portions 111 may be includedproximate one or more discrete features 121.

In some cases, covering 110 and/or one or more customized portions 111may comprise a parameter with a value selected from Range 1, Range 2and/or Range 3 of Table 1 below. Note that the value of one parameterfrom one range may not necessarily be linked to the same range of adifferent parameter.

TABLE 1 Feature Range 1 Range 2 Range 3 Thickness 10 μm to 1 cm 50 μm to500 μm 200 μm to 300 μm Bulk Porosity 0% to 99% 30% to 80% 50% to 70%Length 1 mm to 1 m 3 cm to 50 cm 20 cm to 30 cm Conformality ofConstrictive to loose Restrictive to loose Restrictive - covering 110 tofitting - entire length fitting - entire length or local conduit 120 orlocal portion entire length or local portion thereof thereof portionthereof Compliance under a 0% to 99% 1% to 50% 10% to 25% physiologicload such as arterial pressure Ultimate Strength 0.1 MPa to 500 MPa 0.5MPa to 100 MPa 1 MPa to 10 MPa Biodurability 1 hour to 10 years 48 hoursto 2 years 3 months to 6 months Drug release 1 hour to 10 years 48 hoursto 2 years 3 months to 6 months duration (i.e. when impregnated with adrug or other agent) Macropores (1) Size (1) 10 μm to (1) 20 μm to 200μm (1) 50 μm to 100 μm 1000 μm (2) Spacing (2) 10 μm to (2) 100 μm to500 μm (2) 200 μm to 400 μm 1000 μm Water Permeability 0 mL/cm²/min to50 mL/cm²/min to 100 mL/cm²/min to 300 mL/cm²/min 200 mL/cm²/min 150mL/cm²/min Texture (Roughness 0.025 nm to 50 μm 0.2 μm to 12.5 μm 1.6 μmto 6.3 μm values Ra) Suture retention 0 gf to 1 Kgf 50 gf to 500 gf 100gf to 200 gf strength Kink resistance 0 mm to 1 m 5 mm to 100 mm 10 mmto 20 mm (kink radius) Fiber width and/or 10 μm to 1 mm 20 μm to 500 μm50 μm to 100 μm diameter

In some cases, covering 110 can comprise a compliance, C, that may beequal (e.g. relatively equal) in both axial and tangential directions(C_(axial)=C_(tangential)), such as is described herein in reference toFIG. 1C. In some cases, covering 110 can comprise different axialcompliance than its circumferential (i.e. tangential) compliance, suchas when covering 110 may comprise high circumferential compliance andlow axial compliance (C_(axial)<C_(tangential)), or when covering 110may comprise high axial compliance and low circumferential compliance(C_(axial)>C_(tangential)), such as is described herein in reference toFIG. 1C. In some cases, covering 110 may comprise homogeneous materials,such as materials including homopolymers, copolymers, pure metals and/ormetal alloys. In some cases, covering 110 may comprise compositematerials, such as fiber reinforced, particle reinforced, flakereinforced, multi-layered, and/or segmented materials.

In some cases, material delivery device (MDD) 300 may comprise a deviceconfigured to produce covering 110 by delivering material 350 using anadditive printing process, such as a process similar to that performedby commercially available 3D printers. In some cases, MDD 300 maydeliver material 350 in a series of layers to produce covering 110. Insome cases, MDD 300 may deliver material 350 as a fiber. In some cases,MDD 300 may deliver material 350 onto a surface, such as mandrel 320shown, to produce covering 110, after which covering 110 may bepositioned about conduit 120. In some cases, MDD 300 may producecovering 110 by delivery of material 350 directly onto conduit 120 (e.g.while mandrel 320 may be positioned within conduit 120). In some cases,a first portion of covering 110 may be produced by delivery of material350 onto conduit 120, and a second portion of covering 110 may beproduced by delivery of material 350 onto a surface (e.g. mandrel 320).In some cases, the second portion of covering 110 can subsequently bepositioned about conduit 120 and/or the first portion of covering 110.

In some cases, MDD 300 may comprise a device configured to also producea target (e.g. a template used to produce covering 110), such as whenMDD 300 may create mandrel 320. The outer geometry of mandrel 320 maydefine the inner surface geometry of covering 110, and MDD 300 can beconfigured to produce a customized mandrel 320, such as to create acovering 110 comprising one or more customized portions 111. In somecases, mandrel 320 may be disposed of after the creation of covering110. In some cases, mandrel 320 can be used to create multiple coverings110.

In some cases, MDD 300 may comprise one, two or more devices selectedfrom the group consisting of: a 3D printer; a layer printing device; anelectrospinning device; a melt-spinning device; a melt-electrospinningdevice; a misting assembly; a sprayer; an electrosprayer; a fuseddeposition device; a selective laser sintering device; a fiberdispenser; a wire dispenser; a thread dispenser; a resin depositiondevice, such as a UV-curable resin deposition device; astereolithography device; a phase separation device; a wet spinningdevice; a dip coating device; a lathe; a milling machine; a chemicaletching device; a plasma etching device; a negative mold-over device; aninjection molding device; and any combination thereof. In some cases,MDD 300 and/or other components of system 10 may be constructed andarranged as described herein in reference to FIG. 3. For example, MDD300 can comprise a modification assembly, such as modification assembly605 described herein in reference to FIG. 3, such as to apply orotherwise direct toward covering 110, conduit 120 and/or mandrel 320energy or material selected from the group consisting of: light; heat;cooling; moisture; solvent; drug or other agent; and any combinationthereof.

Material delivery device (MDD) 300 can comprise one, two or more nozzlesor other material delivery elements, nozzle 310. MDD 300 can beconfigured to translate, rotate and/or otherwise reposition nozzle 310along a pathway. Nozzle 310 can comprise two or more concentric nozzles.MDD 300 can be configured to control the delivery of material throughthe one or more nozzles 310, such as to control the speed of material350 delivered to nozzle 310 and/or control the cross sectional shapeand/or area of nozzle 310.

Material 350 may comprise one or more materials configured forimplantation in a patient. Material 350 can comprise one, two or morematerials selected from the group consisting of: synthetic polymer;natural polymer; protein; metal; metal alloy; collagen; elastin; aglycosaminoglycan (e.g. heparin, heparan sulfate, chondroitin sulfate,dermatan sulfate, keratan sulfate, and/or hyaluronic acid); aproteoglycan (e.g. decorin, biglycan, testican, bikunin, fibromodulin,lumican, versican, perlecan, neurocan, aggrecan and/or brevican); analginate; cellulose; gelatin; silk fibroin; fibrinogen; chitosan; anenzyme; fibronectin; glycerin; integrin; keratin; a vitamin; acarbohydrate; a monosaccharide; a disaccharide; a polysaccharide; anucleoside; abductin; lignin; a glycolipid; a phospholipid; a sterol;shrilk; cobalt-chrome; nitinol; aluminum oxide; magnesium; iron; zinc;steel; titanium; vitalium; alacrite; platinum; gold; silver; copper;manganese; a polyester; a polyurethane; a polycarbonate; a polyether; apolysulfone; a polyamide; a polyetheramide; a polystyrene; apolybutadiene; a polyisoprene; a poly(methyl methacrylate); apolyanhydride; a polydimethylsiloxane; a polydioxanone; polyethylene;glycol; polyethylene terephthalate; a polyglycolide; apolyhydroxyalkanoate; polyimide; polytetrafluoroethylene; polyvinylidenefluoride; polyethylene; polypropylene; polyvinylfluoride;polyvinylchloride; polyacylonitrile; silicone; a ceramic; a bioceramic;a bioglass; a composite material and any combination thereof.

As described herein, material delivery device (MDD) 300 can include amandrel or other target, mandrel 320. In some cases, mandrel 320 mayprovide a support structure onto which material 350 may be delivered bynozzle 310. In some cases, conduit 120 may be positioned over mandrel320 and material 350 may be delivered onto conduit 120 while mandrel 320may be in place. In some cases, mandrel 320 may be configured to rotate,translate and/or otherwise move in relation to nozzle 310 (e.g. viamotion of mandrel 320 and/or motion of nozzle 310). In some cases,mandrel 320 may comprise a flat or irregularly shaped surface onto whichmaterial 350 may be delivered to produce covering 110. In some cases,MDD 300 may be configured to produce one or more mandrels 320, such aswhen a subset of mandrels or each mandrel 320 may be disposable (e.g.used for a limited time such as to produce a single covering 110). Insome cases, nozzle 310 can comprise a first nozzle 310 a which may beused to produce a mandrel 320 and a second nozzle 310 b which may beused to apply material 350 onto mandrel 320 to produce covering 110.

In some cases, MDD 300 may comprise a barrier 390, such as a sterilebarrier configured to maintain sterility between one or more portions ofMDD 300 and one or more sterile components of system 10. Barrier 390 cancomprise a sterile drape (e.g. a sterile plastic drape) and/or a moldedsterile covering (e.g. a molded plastic covering). In some cases, one ormore portions of MDD 300 may be sterile (e.g. sterilizable).

Processing unit 200 can comprise one or more electrical or othercomponents, such as one or more of processor 210, memory 220, circuitry230 and/or a user interface (UI) 240, all shown. Processing unit 200 cancomprise one or more algorithms, algorithm 250. Processor 210 cancomprise a microprocessor or other microcontroller configured to performa series of events (e.g. events whose outcome may be determined bystatus of a parameter or outcome of a previous event). Memory 220 cancomprise volatile or non-volatile electronic memory used to temporarilyor permanently store information. In some cases, memory 220 may comprisea library of information. For example, memory 220 can store informationselected from the group consisting of: tissue type; material 350 type;information regarding the application (e.g. clinical application) ofgraft device 100; information regarding use of one or more tools, suchas tool 260 described herein; compliance information; densityinformation; strength information; modulus of elasticity information;elastic limit information; wall thickness information; material 350shrinkage and/or cure time at varying temperature and/or relativehumidity; spacing to mandrel 320 or other target; minimum bend radius ofcovering 110; maximum ovality of covering 110; and any combinationthereof. Construction signal 201 can be based, at least partially, oninformation stored in memory 220. Circuitry 230 may comprise one or moreof analog and/or digital electronic componentry common toelectromechanical, microprocessor controlled equipment.

UI 240 can comprise one or more user input and/or user output componentsselected from the group consisting of: switch; keyboard; membranekeypad; knob; lever; touchscreen; light such as an LED; display; audiotransducer such as a buzzer or speaker; tactile transducer such as aneccentric rotational element; and any combination thereof. In somecases, UI 240 can comprise a display such that an image (e.g. a 2D or 3Dimage) of all or a portion of conduit 120 can be provided to a user ofsystem 10. In some cases, a user can modify the image of conduit 120,via one or more input components of UI 240. In some cases, UI 240 candisplay a proposed (e.g. for modification by the user) or actual (i.e.final) image (e.g. a 2D or 3D image) of all or a portion of covering110. In some cases, construction signal 201 may be at least partiallybased on information provided by a user via UI 240.

User interface (UI) 240 and/or another component of processing unit 200or system 10 can comprise one or more tools configured to allowadjustment of a parameter or other information, tool 260 shown. In somecases, tool 260 may be configured to allow a user to modify anelectronic model of conduit 120 (e.g. a model displayed on UI 240). Insome cases, tool 260 may be configured to allow a user to modify anelectronic model of covering 110 (e.g. a proposed or final model ofcovering 110 that may be displayed on UI 240). In some cases, tool 260may provide a property modifying function selected from the groupconsisting of: smooth; erase; spline; fillet, fill; insert a buildingblock (e.g. a geometric structure to the model); and any combinationthereof. In some cases, tool 260 may be configured to allow a user toinsert a building block comprising an electronic model selected from thegroup consisting of: anastomosis; dimple (e.g. to accommodate asidebranch); reinforcing spline; and any combination thereof In somecases, tool 260 may be configured to measure a distance (e.g. a length,width, diameter, taper, radius of curvature and/or thickness).

In some cases, a user of system 10 may enter information via UI 240, andconstruction signal 201 may be based at least in part on thatinformation. For example, a user can enter information that creates acustomized portion 111 and/or positions a customized portion 111 alongcovering 110. In some cases, algorithm 250 may produce a constructionsignal 201 that may be based both on image data 410 and informationprovided by a user via UI 240.

Algorithm 250 can be configured to analyze one or more portions of imagedata 410 and may produce construction signal 201 based on the analysis.The analysis of image data 410 by algorithm 250 can include analysis ofother information, such as information stored in memory 220 and/orinformation provided by a user via user interface (UI) 240. Using imagedata 410 and/or such other information, algorithm 250 can producemathematical models, geometric models, thresholds, boundary conditionsand other information relevant to the creation of construction signal201. In some cases, construction signal 201 may be based on both imagedata 410 and other information, such as information stored in memory 220and/or information input by a user of system 10 via UI 240. In somecases, algorithm 250 may be configured to produce a spatial model and/orother three-dimensional model of conduit 120 based on image data 410(e.g. image data including multiple slices of a CT image or othermulti-dimensional information produced by imaging device 400). In somecases, a user of system 10 can modify the three-dimensional model ofconduit 120, such as by using one or more controls or tools of UI 240.

In some cases, algorithm 250 may be configured to produce a point cloud,surface model and/or other three-dimensional model of a “proposed”covering 110, such as to enable one or more modifications of the modelto be made prior to producing a construction signal 201 used to producecovering 110 for graft device 100. The one or more modifications of themodel can be performed automatically by algorithm 250 (e.g. based on oneor more identified discrete features 121 of conduit 120) and/or manuallyby a user of system 10 (e.g. based on user input). In some cases,algorithm 250 may be configured to produce a model of a covering 110(proposed and/or final), based on one or more boundary conditions (e.g.to optimize hemodynamics by reducing flow turbulence, controllingbending radius, controlling lumen geometry; controlling a transition;controlling a taper; controlling a bend portion; controlling tortuosity;controlling wall shear; preventing buckling, optimizing wall shearstress; modifying an end portion to optimize an anastomotic connection;and/or reducing geometric mismatch near an anastomotic connection). Insome cases, algorithm 250 may be configured to convert data from animaging coordinate system (e.g. coordinate system of imaging device 400and/or image data 410) to data in a material deposition coordinatesystem (e.g. a coordinate system of MDD 300). In some cases, the imagingcoordinate system may comprise a Cartesian coordinate system and thematerial deposition coordinate system may comprise a cylindrical,spherical and/or curvilinear coordinate system.

In some cases, algorithm 250 may be configured to identify a feature ofconduit 120, such as feature 121 described herein. Algorithm 250 can beconfigured to create (e.g. via construction signal 201) a customizedportion 111 of covering 110, the customized portion 111 surrounding orat least proximate that particular feature 121 of conduit 120. A subsetof customized portions or each customized portion 111 can comprise aproperty that is different than another portion of covering 110 (e.g.different than the majority of covering 110). Customized portion 111 cancomprise one, two or more portions that have a differentiating propertyselected from the group consisting of: different (e.g. increased and/ordecreased) thickness; different material; different porosity; differentpore size; different compliance in one or more directions (e.g. axiallyand/or radially); different level of conformality; different texture;different alignment and/or orientation of material (e.g. fiber)deposition); different stiffness; different fiber diameter; addition ofa kink-resisting element; addition of an agent such as a growth factoror pharmaceutical agent; and any combination thereof.

In some cases, covering 110 may comprise one or more customized portions111 which may be customized to cover a protrusion (e.g. a sidebranch orother protrusion) of conduit 120 and/or a ligation device may be used toocclude a sidebranch of conduit 120, such as sidebranch-accommodatingportion 111 a shown. Portion 111 a can have a geometry configured toaccommodate the sidebranch and/or a ligation device without compromisingan internal lumen of conduit 120, such as by creating a space (e.g. arecess or hole in covering 110) in which the sidebranch and/or ligationdevice may be located. In some cases, one or more customized portions111 positioned proximate a sidebranch can comprise one or more of: aportion comprising a change (e.g. an increase) in deposition of material350 such as to mechanically reinforce and/or provide a strain relief ata sidebranch location; a portion configured to constrain a sidebranchsuch as to minimize hemodynamic disruption in a lumen of conduit 120(e.g. to cause a slightly greater restriction around bulboussidebranches or varicosity to force more material towards the lumen andreduce irregularities within the lumen); and any combination thereof. Insome cases, a customized portion 111 can include at least a portion thatis positioned away from but proximate a sidebranch location, such as aportion of conduit 120 that may include a void region (e.g. a holeand/or recess), such as when algorithm 250 produces a constructionsignal 201 that may include a customized portion 111 that fills the voidproximate the sidebranch.

In some cases, covering 110 may comprise one or more customized portions111 which comprise a fillet (i.e. rounded interior corner) of covering110, such as fillet portion 111 b shown and positioned in covering 110to be located proximate a sidebranch location of conduit 120 whencovering 110 may be positioned about conduit 120.

In some cases, covering 110 may comprise one or more customized portions111 which may be positioned proximate to (e.g. on or near), or otherwisepositioned relative to, a discrete feature 121 comprising an end ofcovering 110, such as a customized portion 111 to be positionedproximate an end of conduit 120 when covering 110 may be positionedabout conduit 120. For example, customized portion 111 can comprise atapered portion of covering 110, such as tapered portion 111 c shown.Tapered portion 111 c can be positioned at one or more ends of covering110, such as to create a non-conforming portion of customized portion111 (e.g. a space exists between covering 110 and conduit 120 at taperedportion 111 c, such as to allow for radial expansion of conduit 120 atthat location). In some cases, customized portion 111 can comprise areinforced portion (e.g. a thicker portion or a portion including moredurable materials), such as reinforced portion 111 d shown. Reinforcedportion 111 d can be positioned at one or more ends of covering 110, andcan be combined with tapered portion 111 c at either or both ends. Insome cases, one or more reinforced portions 111 d may be positionedabout a mid-portion of covering 110, or at any feature 121 of conduit120, such as when a reinforced portion 111 d may be positioned at athin-walled portion of conduit 120. In some cases, a customized portion111 to be located proximate an end of conduit 120 can be optimized foran anastomotic connection, such as to include an optimized shape (e.g.optimized shape for an anastomosis), optimized structural support,optimized material, optimized permeability, optimized porosity,optimized thickness, optimized biodurability, inclusion of agents suchas growth factors or pharmaceutical drugs to be delivered to anastomosisand/or other optimized characteristic for performing and maintaining ananastomotic connection. In some cases, conduit 120 and its associatedcovering 110 may comprise three or more ends, such as when a bifurcated,trifurcated or other multiple branched graft device may be beingconstructed. One of more ends, such as each end (such as each of threeor more ends) can include a customized portion 111 as described herein.In some cases, tapered portion 111 c, reinforced portion 111 d and/oranother customized portion 111 can be configured as a strain-relief,such as a strain relief to be located proximate an end or bend portionof graft device 100.

Image data 410 can include information related to the compliance of oneor more portions of conduit 120, such as when algorithm 250 may identifya discrete feature 121 comprising tissue whose softness and/orflexibility may be above a threshold. In some cases, a customizedportion 111 can comprise material, compliance, thickness, permeability,porosity and/or anisotropy that is different than other portions ofcovering 110. Algorithm 250 can analyze image data 410 and identify oneor more shape changes of conduit 120 that occur over time (e.g. apre-harvested, in-situ conduit 120 that may change shape due to changein blood pressure, respiration and/or patient movement). In some cases,customized portion 111 can comprise an expandable geometry, a“loose-fitting” geometry and/or a compliance matching that of conduit120. Algorithm 250 can analyze image data 410 and identify a customizedportion 111 of covering 110 that has a modified (e.g. increased and/ordecreased) porosity. For example, covering 110 may have a customizedportion 111 of modified porosity proximate a discrete feature 121 ofconduit 120, such as a discrete feature 121 comprising an anastomosissite (e.g. an end portion of conduit 120), and/or a segment of highcurvature. Algorithm 250 can analyze image data 410 and identify acustomized portion 111 of covering 110 that may have a modifiedcompliance (e.g. increased and/or decreased compliance in a radialand/or axial direction). For example, covering 110 may have a portion111 of modified compliance proximate a discrete feature 121 of conduit120, such as a discrete feature 121 comprising an anastomosis site (e.g.an end portion of conduit 120 or a mid-portion for a side-to-sideanastomosis), a ligament and/or tendon attachment site (e.g. when graftdevice 100 comprises an implant configured to function as ligamentand/or a tendon), a site of segmented compliance (e.g. for radialreinforcement, kink resistance and/or peristaltic flow), and/or anycombination thereof.

In some cases, algorithm 250 may be configured to create and/or modify(generally “create”) a pathway of motion of a material delivery portionof MDD 300 (e.g. nozzle 310). For example, algorithm 250 can beconfigured to avoid one or more “off limits” locations, such aspositions to be avoided that are stored in memory 220. In some cases,algorithm 250 may be configured to create a pathway of motion that mayavoid one or more portions of system 10, as described by way of exampleherein. Algorithm 250 can be configured to create a pathway of motionthat may avoid previously-produced partial portions of covering 110while completing the production of covering 110. As described above, insome cases, covering 110 may be produced by delivery of material 350onto conduit 120. In some cases, algorithm 250 can be configured tocreate a pathway of motion that avoids contact with conduit 120. Asdescribed above, in some cases, covering 110 may be produced by deliveryof material 350 onto and/or at least toward a surface or tube, such asmandrel 320 described above (e.g. with or without conduit 120 in place).In some cases, algorithm 250 can be configured to create a pathway ofmotion that avoids contact with mandrel 320.

As described above, in some cases, covering 110 may be produced bydelivery of material 350 onto conduit 120. In some cases, algorithm 250can be configured to create a pathway of motion that avoids damaging(e.g. thermally damaging) conduit 120 (e.g. when the delivery ofmaterial 350 is at an elevated temperature), such as by minimizing heatdissipation to conduit 120 during delivery of material 350. For example,algorithm 250 can be configured to create a pathway of motion thatavoids multiple passes of delivery of material 350 onto conduit 120 inneighboring regions within a time period (i.e. to allow cooling orotherwise avoid undesired accumulation of thermal energy in any onesmall portion of conduit 120).

In some cases, algorithm 250 may be configured to perform aself-diagnostic. Algorithm 250 can be configured to perform aself-diagnostic, such as a self-diagnostic based on signals from one ormore sensors of system 10, such as a sensor 209 of processing unit 200,a sensor 309 of material delivery device (MDD) 300 and/or a sensor 409of imaging device 400. Sensors 209, 309 and/or 409 may individually orany combination thereof comprise one or more sensors selected from thegroup consisting of: an optical sensor; a laser; a magnetic sensor; anelectrical sensor; an energy sensor; a pressure sensor; a force sensor;a strain gauge; a position sensor; a flow sensor; a sound sensor; anultrasound sensor; a humidity sensor; and any combination thereof. Forexample, algorithm 250 can perform a self-diagnostic to assess aparameter of MDD 300 selected from the group consisting of: electricalconnection status; rotational speed; translational speed; nozzle 310status; material delivery status; temperature (e.g. via a thermocoupleof other sensor of system 10); chamber environment condition (e.g.temperature or relative humidity as measured by a sensor of system 10);energy delivered (e.g. laser energy delivered); home position; adistance between two components of MDD 300; and any combination thereof.

Referring additionally to FIG. 1A, a side sectional view of a graftdevice comprising a covering including multiple customized portions isillustrated. Covering 110 may be positioned about conduit 120. In somecases, covering 110 may be produced by MDD 300 delivery of materialdirectly on conduit 120. In some cases, covering 110 can be produced byMDD 300 separate from conduit 120 (e.g. onto mandrel 320 or othersurface), and subsequently positioned about conduit 120. In some cases,covering 110 may have an internal profile that conformally surroundsconduit 120, such as is shown in FIG. 1A except in the area of thecustomized portion, tapered portion 111 c. In some cases, there may bespace between one or more portions of covering 110 and conduit 120, suchas one or more spaces positioned proximate one or more ends of conduit120 (e.g. to allow expansion of an end portion or other portion ofconduit 120 prior to contacting covering 110), such as is shown attapered portion 111 c.

In some cases, covering 110 may comprise fibers that are oriented toprovide constraint against radial expansion that may be greater than theconstraint against axial expansion, such as by aligning fibers ofcovering 110 more in the radial direction than in the axial direction.

Referring additionally to FIG. 1B, a side sectional view of a graftdevice comprising a covering including a large proportion ofisotropically oriented fibers is illustrated. Covering 110 is shownpositioned about conduit 120, such as when material 350 is delivereddirectly onto conduit 120 and/or when covering 110 may be produced andsubsequently placed about conduit 120. Covering 110 of FIG. 1B mayinclude at least a portion comprising a matrix of fibers whoseorientation may be primarily isotropic, such that expansion in alldirections may be relatively uniform.

Referring additionally to FIG. 1C, a side sectional view of a graftdevice comprising a covering including a larger proportion ofcircumferentially oriented fibers is illustrated. Covering 110 is shownpositioned about conduit 120, such as when material 350 may be delivereddirectly onto conduit 120 and/or when covering 110 may be produced andsubsequently placed about conduit 120. Covering 110 of FIG. 1C mayinclude at least a portion comprising a matrix of fibers whoseorientation is primarily in a relatively circumferential direction, suchthat expansion of covering 110 (and graft device 100) may be morelimited in a radial direction than in an axial direction.

Referring now to FIG. 2, a flow chart of a method for producing a graftdevice is illustrated. Method 1000 may comprise a series of steps ofproducing a graft device using system 10 described herein in referenceto FIG. 1. In STEP 1010, an image of a conduit 120 (e.g. a blood vesselor other tubular conduit) may be made, such as via imaging device 400 toproduce image data 410. In STEP 1020, processing unit 200 may receivethe image data 410, such as to create a 3D electronic model (e.g. a CADor other electronic model) of conduit 120. In some cases, an STEP 1025may be performed, in which the 3D electronic model of conduit 120 may bemodified, such as automatically by algorithm 250 and/or manually by auser of system 10 via user interface (UI) 240.

In STEP 1030, an electronic model of a proposed covering 110 may becreated by processing unit 200. In some cases, algorithm 250 may createthe electronic model of the proposed covering 110 based on informationselected from the group consisting of: identified discrete features 121of conduit 120; information stored in memory 220; information input by auser via UI 240; and any combination thereof. In some cases, an STEP1035 may be performed, in which the electronic model of the proposedcovering 110 may be adjusted, such as an adjustment performed by a userof system 10 via UI 240.

In STEP 1040, covering 110 may be produced by material delivery device(MDD) 300. In some cases, covering 110 may be produced by delivery ofmaterial 350 directly onto conduit 120. In some cases, covering 110 maybe produced separate from conduit 120 (e.g. on a surface, tube or othermandrel 320), and subsequently positioned about conduit 120 (e.g. in theSTEP 1045). In some cases, a mandrel 320 may be produced by MDD 300 asdescribed herein.

Referring now to FIG. 3, a schematic view of a system for producing animplantable device is illustrated. System 10 may include variouscomponents and assemblies (hereinafter “components”) used to produce animplantable device, such as graft device 100 shown. System 10 maycomprise processing unit 200, material delivery device (MDD) 300 andimager 400, and one or more of these can be of similar construction andarrangement and/or include similar components to those described hereinin reference to FIG. 1. Imager 400 may comprise an imaging device andmay produce image data 410. Image data 410 can represent geometric andother information related to conduit 120 (e.g. a blood vessel, othertubular conduit and/or other patient tissue) and/or any portion of apatient's anatomy. Processing unit 200 can include algorithm 250, whichcan be used to produce a construction signal 201 based on the image data410. MDD 300 can comprise a material delivery device used to produce animplantable device that is based on construction signal 201. Forexample, MDD 300 can deliver one or more materials, material 350, toproduce an implantable device, and the pattern of the delivery of thematerial 350 can be based on construction signal 201 (andcorrespondingly based on image data 410). In some cases, MDD 300 mayproduce a covering 110 which may be positioned about conduit 120 toproduce graft device 100. Covering 110 can be positioned about conduit120 after covering 110 may be produced by MDD 300, or MDD 300 candeliver material 350 directly onto conduit 120 while producing covering110.

Graft device 100 can be constructed and arranged to perform or otherwisefunction as a bypass graft, such as a coronary artery bypass graft or aperipheral artery bypass graft. In some cases, graft device 100 isconstructed and arranged as a neo-vessel, such as a neo-artery and/or aneo-vein. Conduit 120 can include living tissue and/or artificialmaterials. In some cases, conduit 120 may comprise living tissue (e.g.harvested tissue), such as a segment or other portion of tissue selectedfrom the group consisting of: saphenous vein; vein; artery; urethra;intestine; esophagus; ureter; trachea; bronchi; duct; fallopian tube;and any combination thereof or other tissues. In some cases, conduit 120can comprise an artificial material selected from the group consistingof: polytetrafluoroethylene (PTFE); expanded PTFE (ePTFE); polyester;polyvinylidene fluoride/hexafluoropropylene (PVDF-HFP); silicone;polyethylene; polypropylene; polyester-based polymer; polyether-basedpolymer; thermoplastic rubber; and any combination thereof or othermaterials. Graft device 100 may comprise first end 101, second end 102,and a lumen 103 extending from first end 101 to second end 102. System10 may include a material delivery device, MDD 300, may be configured todeliver material 350 to produce covering 110. Material 350 can comprisea biocompatible material such as a biocompatible metal and/or plastic.Material 350 can comprise a first material 351 (e.g. a polymer) and asecond material 352 (e.g. a solvent).

Material delivery device (MDD) 300 can comprise a 3D printing device. Insome cases, MDD 300 may comprise a device selected from the groupconsisting of: a 3D printer; a layer printing device; an electrospinningdevice; a melt-spinning device; a melt-electrospinning device; a mistingassembly; a sprayer; an electrosprayer; a fused deposition device; aselective laser sintering device; a fiber dispenser; a wire dispenser; athread dispenser; a resin deposition device, such as a UV-curable resindeposition device; a stereolithography device; a phase separationdevice; a wet spinning device; a dip coating device; a lathe; a millingmachine; a chemical etching device; a plasma etching device; a negativemold-over device; an injection molding device; and any combinationthereof. In some cases, MDD 300 may comprise a second material deliverydevice, such as a material delivery device selected from the groupconsisting of: an electrospinning device; a melt-spinning device; amelt-electrospinning device; a misting assembly; a sprayer; anelectrosprayer; a fuse deposition device; a selective laser sinteringdevice; a three-dimensional printer; and any combination thereof. Insome cases, second material 352 or another portion of material 350 maycomprise a solvent or other material that may be desired to be removedbefore covering 110 may be implanted in the patient. In some cases,system 10 can be configured to remove second material 352 (e.g. asolvent), accelerate the removal of second material 352 and/or at leastreduce the amount of second material 352 present in conduit 120,covering 110, graft device 100, chamber 20 and/or another component ofsystem 10 (hereinafter “remove second material 352” or “removesolvent”). In some cases, system 10 can be configured to reduce injuryto the conduit 120 by one or more solvents (e.g. reduce injury to livingtissue such as living vein tissue). System 10 can include one or moresensors, such as sensors 26, 36, 329, 309, 369 and/or 606 shown anddescribed in detail herein. Sensors 26, 36, 329, 309, 369 and/or 606 canprovide a signal related to the creation of covering 110 (e.g. relatedto the presence of one or more solvents and/or a signal otherwise usedto perform a solvent-reducing process and/or to reduce injury to aconduit 120 by one or more solvents).

System 10 can include a mandrel 320 and a material delivery device (MDD)300 can comprise a rotating assembly 340 configured to rotate mandrel320. In the embodiment shown in FIG. 3, mandrel 320 may be slidinglyinserted into conduit 120, and subsequently engaged with rotatingassembly 340. In some cases, covering 110 may be produced on mandrel 320(e.g. material 350 is delivered onto mandrel 320), as described hereinin reference to FIG. 1. In some cases, covering 110 may be producedwithout the use of mandrel 320. MDD 300 can include material dispenser301 configured to dispense one or more materials, such as material 350shown. Material 350 can comprise one or more materials as describedherein in reference to FIG. 1. Material 350 can include a mixture of oneor more first materials 351 (e.g. one or more polymers), one or moresecond materials 352 (e.g. one or more solvents) and/or other materialsused to produce covering 110. Material 350 can comprise a cartridge orother reservoir surrounding first material 351 and/or second material352, the reservoir being fluidly attachable to material dispenser 301 byan operator of system 10.

System 10 can include an environmentally controllable chamber, chamber20 shown, which surrounds at least a portion of mandrel 320 (e.g.surrounding at least conduit 120 and covering 110 during the creation ofgraft device 100). Chamber 20 can surround one or more portions ofmaterial delivery assembly 305 and/or modification assembly 605described herein. In some cases, chamber 20 may comprise a disposablecartridge and/or at least a portion of chamber 20 is disposable (e.g.used to create implants for a single patient). Chamber 20 can beconfigured to remove solvents or other potentially harmful materials(collectively “remove solvent” herein) during and/or after production ofcovering 110.

System 10 may include controller 30 which is configured to providecontrol signals and/or receive information signals. Controller 30 can beconfigured to control one or more of: material delivery assembly 305(e.g. to control the flow rate of material 350 into material deliveryassembly 305); rotating assembly 340 (e.g. to control the rotation ofmandrel 320); linear drive assembly 345 (e.g. to control the translationrate or position of material delivery assembly 305); modificationassembly 605 (e.g. to control delivery of material by modificationassembly 605, delivery of energy by modification assembly 605 and/orremoval of a portion of covering 110 by modification assembly 605);linear drive assembly 645 (e.g. to control the translation rate orposition of modification assembly 605); voltage applied to mandrel 320(e.g. voltage provided by power supply 302); and any combinationthereof. Controller 30 can comprise environmental controller 35.Environmental controller 35 can be configured to remove solvents. Insome cases, environmental controller 35 can be configured to control anenvironmental parameter within chamber 20, such as an environmentalparameter selected from the group consisting of: temperature; humidity;pressure; solvent concentration; and any combination thereof.Environmental controller 35 or another component of controller 30 cancomprise one or more fans or other gas propulsion mechanisms, such as toprovide air or other gas to inlet port assembly 21 (e.g. via the tubeshown positioned between controller 30 and inlet port assembly 21) orextract gas from chamber 20 via outlet port assembly 22 (e.g. via thetube shown positioned between controller 30 and outlet port assembly22). In some cases, controller 30 may comprise an alarm assembly, whichcan be constructed and arranged to be activated when an undesired statemay be detected (e.g. an undesired concentration or amount of solventpresent, or other undesired state related to a solvent), such as tonotify an operator of system 10. Controller 30 can comprise an alarmassembly constructed and arranged to provide an alert selected from thegroup consisting of: audible alert; visual alert; tactile alert; and anycombination thereof. In some cases, when an undesired state may bedetected (e.g. an unacceptable concentration of solvent within chamber20, within conduit 120 and/or within covering 110 is detected), creationof covering 110 by system 10 may be stopped.

In some cases, system 10 may comprise one or more similar or dissimilarspines 510, and graft device 100 may comprise one or more of the spines510. In some cases, material delivery device (MDD) 300 may be configuredto produce spine 510, such as when MDD 300 may comprise at least a 3Dprinter. System 10 can include spine application tool 500, which cancomprise a manual or automated (e.g. robotic) tool used to place spine510 about conduit 120, such as between one or more layers of covering110 (e.g. between an inner layer with a first thickness, and an outerlayer with a second thickness about twice as thick as the first layer'sthickness). In some cases, system 10 can include one or more tools,components, assemblies and/or otherwise be constructed and arranged asdescribed in applicant's co-pending U.S. patent application Ser. No.15/023,265, filed Mar. 18, 2016, the content of which is incorporatedherein by reference in its entirety for all purposes.

In some cases, a system for producing a graft device may comprise atubular conduit; a first spine; and a fiber matrix delivery assemblyconstructed and arranged to deliver a fiber matrix to surround thetubular conduit.

In some cases, a system may comprise a second spine. The first spine cancomprise a first inner diameter and the second spine can comprise asecond inner diameter different than the first inner diameter. The firstinner diameter and the second inner diameter can comprise approximatediameters selected from the group consisting of: about 4.0 mm; about 4.7mm and about 5.5 mm. The system can comprise a third spine. The firstspine can comprise a first inner diameter, the second spine can comprisea second inner diameter different than the first inner diameter, and thethird spine can comprise a third inner diameter different than the firstinner diameter and the second inner diameter. The first inner diametercan comprise a diameter of about 4.0 mm, the second inner diameter cancomprise a diameter of about 4.7 mm and the third inner diameter cancomprise a diameter of about 5.5 mm.

In some cases, the system may comprise a spine application toolconstructed and arranged to apply a spine about the tubular conduit. Thespine application tool can be constructed and arranged to laterallyapply the spine about the tubular conduit. The fiber matrix can comprisean inner layer and an outer layer, and the spine application tool can beconstructed and arranged to apply the spine between the inner and outerlayer of the fiber matrix. The spine application tool can comprise anautomated tool. The spine application tool can comprise a robotic tool.The fiber matrix delivery assembly can comprise the spine applicationtool. The spine application tool can comprise a scissor-likeconstruction.

In some cases, the system may comprise a trimming tool constructed andarranged to trim one or both ends of the spine. The trimming tool can beconstructed and arranged to trim the fiber matrix. The trimming tool cancomprise a tool selected from the group consisting of: scissors;scalpel; laser cutter; radiofrequency cutter; and any combinationthereof. The fiber matrix delivery assembly can comprise the trimmingtool. The trimming tool may comprise an automated tool. The trimmingtool may comprise a robotic tool. The fiber matrix delivery assembly cancomprise the trimming tool. The trimming tool can comprise a laser. Insome cases, the system may comprise a surface modifying agent.

In some cases, the system may comprise a spine fabrication toolconstructed and arranged to produce the spine. The spine fabricationtool can comprise a rod and a plurality of pins. The rod can comprise arelatively linear rod. The rod can comprise at least a non-linearportion. The fiber matrix delivery assembly can comprise the spinefabrication tool. The fiber matrix delivery assembly can comprise an electrospinning device constructed and arranged to produce the spine. Thefiber matrix delivery assembly can comprise a three-dimensional printerconstructed and arranged to produce the spine. The fiber matrix deliveryassembly can comprise a stereolithography device constructed andarranged to produce the spine. The fiber matrix delivery assembly maycomprise a fuse deposition device constructed and arranged to producethe spine.

Also provided herein may be systems and methods for producing a graftdevice commising a conduit, a surrounding fiber matrix and a spine.Systems may include an el ectrospinning device and/or other fiber orfiber matrix delivering assembly. In some cases, the spine may comprisea component that may be applied, placed andlor inserted, such as by thefiber matrix delivery assembly (e.g. automatically orsemi-automatically) or with a placement or insertion tool (e.g.manually).

System can include a tool for applying spine about conduit, such asspine application tool constructed and arranged to engage an innerand/or outer portion of spine and subsequently cause spine to radiallyexpand to be placed (e.g. laterally placed) about conduit. In somecases, tool can be constructed and arranged to maintain the geometry(e.g. shape or alignment) of one or more spines, such as to maintain thegeometry of one or more spines during shipping and/or storage.

System can include one or more agents for modifying the surface ofspine, conduit and/or a fiber matrix applied by fiber matrix deliveryassembly.

System can include one or more tools for cutting or otherwise trimmingone or more spines to a particular length, such as trimming tool. Spineand one or more portions of an applied fiber matrix can be trimmed priorto, during or after application of one or more polymers from polymersolution dispenser by fiber matrix delivery assembly. Trimming tool canbe a manual tool and/or an at least partially automated tool, such as atool integrated into fiber matrix delivery assembly. In some cases, atrimming tool may comprise one or more cutting tools such as a cuttingtool selected from the group consisting of: scissors; scalpel; lasercutter; radiofrequency cutter; and combinations thereof.

System can include one or more fasteners configured to apply a retentionforce between at least two of tubular conduit, spine and an appliedfiber matrix comprising one or more polymers from polymer solutiondispenser. Fasteners can comprise one or more elements selected from thegroup consisting; of: adhesive; staple; clip; suture; barb; hook; andany combination thereof. In some cases, fasteners comprise at leastabout 4 fasteners. In some cases, one or more fasteners may be attachedto and/or attachable to spine. Fasteners can be applied to conduitand/or spine when conduit and/or spine are positioned about mandrel.Fasteners can be positioned within about 1 cm of one or both ends ofconduit. In some cases, one or more fasteners may comprise a materialsimilar to the material of spine, such as the material of aninterdigitating projection of spine as described herein.

System can include spine fabrication tool which may be constructed andarranged to produce one or more spines. Spine fabrication tool can beconstructed and arranged to resiliently bias spine, such as in arelatively linear or non-linear shape. In some cases, a spinefabrication tool may be integral to fiber matrix delivery assembly. Insome cases, a fiber matrix delivery assembly can create the spine withan assembly selected from the group consisting of: an electrospinningdevice; a three-dimensional printer; a stereolithography device; a fusedeposition device; and any combination thereof. In some cases, a spinefabrication tool may be a separate device. In some cases, a spinefabrication tool may comprise one or more rods about which a filament iswrapped to create spine, such as two or more rods with different outerdiameters used to produce two or more spines with different innerdiameters.

A system can include one or more patterning masks, such as a physical orchemical mask used to prevent fiber matrix from covering one or moreportions of conduit. In some cases, a system may include an apertureplate. Aperture plate can comprise a stencil-like pattern configured toprevent or reduce delivery of fiber to certain portions of the outersurface of conduit. In some cases, an aperture plate can comprise astencil-like pattern that causes fiber matrix to include a pattern ofrelief slots. In some cases, an aperture plate can be configured toinduce one or more changes to the electromagnetic (EM) field withinelectrospinning device. These one or more changes to the EM field can beconfigured to cause variations in the delivered fiber pathway, resultingin a patterned fiber matrix. In some cases, a mandrel can have modifiedelectrical characteristics, such as modified conductivity along itslength, configured to modify the EM field to cause patterned fiberdeposition.

A system can include a power supply, power supply may be configured toprovide the electric potentials to nozzle and mandrel, as well as tosupply power to other components of system such as drive assemblies andand modification assembly. Power supply can be connected, eitherdirectly or indirectly, to at least one of mandrel and conduit. Powercan be transferred from power supply to each component by, for example,one or more wires.

A system can include inlet and/or outlet ports. Ports may be configuredto control the environment surrounding the environment surroundingmandrel. A port can be configured to be both an inlet port and an outletport. A system can include a housing. A housing may be attachable toelectrospinning device and defining a chamber surrounding assembliesand/or and/or mandrel, such that the ports can control a more limited(smaller) environment surrounding assemblies and/or and/or mandrel. Insome cases, the ports can be used to introduce or remove one or moregases, introduce or remove humidity, control temperature, controlsterility, provide other environmental controls, and any combinationthereof.

Mandrel 320 can comprise a metal mandrel, such as a mandrel constructedof 304 or 316 series stainless steel. Mandrel 320 can comprise amirror-like surface finish, such as a surface finish with an R_(a) ofabout 0.1 micrometers (μm) to about 0.8 μm. Mandrel 320 can comprise alength of up to about 45 centimeters (cm), such as a length of fromabout 30 cm to about 45 cm, or from about 38 cm to about 40 cm. In somecases, system 10 may include multiple mandrels 320 with multipledifferent geometries, such as a set of mandrels 320 with differentdiameters (e.g. diameters of about 3.0 millimeter (mm), about 3.5 mm,about 4.0 mm, and/or about 4.5 mm). In some cases, MDD 300 may beconfigured to automatically detect the mandrel 320 diameter (e.g. and toadjust rotation rate and/or another system parameter based on thedetected mandrel 320 diameter). One or both ends of mandrel 320 may beinserted into driving elements of rotating assembly 340, motors 341 aand 341 b, respectively, such that mandrel 320 can be rotated about axis335 during creation of covering 110. In some cases, a single motor maydrive one end of mandrel 320, with the opposite end attached to arotatable attachment element (e.g. a bearing) of MDD 300.

Mandrel 320 can comprise a porous mandrel, such as a mandrel configuredto deliver one or more drugs or other agents to covering 110 and/orconduit 120 prior to, during and/or after creation of covering 110. Insome cases, an agent 602 may be delivered to (e.g. coated onto) covering110 and/or conduit 120 via a porous mandrel 320, via material deliveryassembly 305 (e.g. via nozzle 310), via modification assembly 605 (e.g.via modifying element 627), or otherwise. Agent 602 can comprise asolvent-reducing material (e.g. a material configured to absorb solventand a material configured as a barrier that prevents solvent fromreaching covering 110 and/or conduit 120), a solvent neutralizingmaterial, a hydrating solution and/or a preservative solution. In somecases, agent 602 may comprise a preservative solution comprising one ormore materials selected from the group consisting of: chilled fluid;fluid chilled to about 4° C.; water; saline; heparin; heparinizedsaline; blood; ringers solution; and any combination thereof. In somecases, agent 602 may comprise a material configured as both a barrierand a solvent-absorbing material.

MDD 300 can include one or more material delivery assemblies, and in theillustrated embodiment, MDD 300 may include material delivery assembly305. Material delivery assembly 305 may comprise nozzle 310. Nozzle 310may include an orifice constructed and arranged to deliver material 350to produce covering 110. Nozzle 310 can be a tubular structure includingnozzle central axis 328. Nozzle 310 can be constructed of stainlesssteel, such as passivated 304 stainless steel. In some cases, nozzle 310may comprise an outer tube and an inner tube, such as to avoid icicleformation about nozzle 310. For example, material delivery assembly 305and/or nozzle 310 can be constructed and arranged as described inapplicant's co-pending application U.S. patent application Ser. No.15/036,304, filed May 12, 2016.

Electrospinning device can include one or more nozzle assemblies. Insome cases, an electrospinning device may include nozzle assembly, whichmay include one or more nozzles. Nozzle assembly may be fluidly attachedto polymer solution dispenser via delivery tube. Dispenser may comprisea solution of one or more polymers, solvents and/or other materials.Nozzle assembly may be operably attached to a linear drive assemblyconfigured to translate nozzle assembly in at least one direction.

In some cases, a modifying element may comprise a nozzle, such as anozzle configured to deliver a fiber modifying agent and/or a graftmodifying agent. A reference to a “nozzle” and “nozzle assembly” insingular or plural form can include one or more nozzles, such as nozzle,and one or more assemblies, such as nozzle assemblies.

Nozzle can be constructed of stainless steel. In some cases, nozzle mayhave a tubular construction with a length of about 1.5 inches, an innerdiameter (ID) of about 0.047 inches and an outer diameter (OD) of about0.065 inches. Nozzle can include an insulating coating, with the tip ofnozzle exposed (e.g. non-insulated), such as with an exposed length ofabout 1 centimeter (cm). Nozzle geometry and electrical potentialvoltages applied between nozzle and mandrel may be chosen to controlfiber generation. In some cases, fibers may be produced with an averagediameter from about 1.0 micrometer (μm) to about 20 μm, such as fromabout 5 μm to about 15 μm, or from about 6 μm to about 12 μm.

A mandrel may be positioned in a particular spaced relationship fromnozzle assembly and/or modification assembly, and nozzle and/ormodifying element, respectively. In some cases, a mandrel may bepositioned above and below assemblies and, respectively. In some cases,a mandrel can be positioned either above, below, to the right and/or orto the left of, assembly and/or assembly. The distance between mandreland the tip of nozzle and/or modifying element can be less than about 20cm, or less than about 15 cm. In some cases, the tip of nozzle and/ormodifying element may be about 12.5 cm from mandrel. In some cases,multiple nozzles and/or multiple modifying elements, for examplecomponents of similar or dissimilar configurations, can be positioned invarious orientations relative to mandrel. In some cases, the distancebetween nozzles and/or modifying elements and mandrel may vary along thelength of mandrel, such as to create a varying pattern of fiber matrixalong conduit. In some cases, a nozzle and/or modifying elementdistances from mandrel can vary continuously during the electrospinningprocess and/or the distance can vary for one or more set periods of timeduring the process.

In some cases, an electrical potential may be applied between nozzle andone or both of conduit and mandrel. The electrical potential can draw atleast one fiber from nozzle assembly to conduit. Conduit can act as thesubstrate for the electrospinning process, collecting the fibers thatmay be drawn from nozzle assembly by the electrical potential. In somecases, a mandrel and/or conduit may have a lower voltage than a nozzleto create the desired electrical potential.

In some cases, a polymer solution, stored in polymer solution dispenser,may be delivered to nozzle assembly through polymer solution deliverytube. The electrical potential between nozzle and conduit and/or mandrelcan draw the polymer solution through nozzle of nozzle assembly.Electrostatic repulsion that may be caused by the fluid becoming chargedfrom the electrical potential, may counteract the surface tension of astream of the polymer solution at nozzle of the nozzle assembly. Afterthe stream of polymer solution may be stretched to its critical point,one or more streams of polymer solution may emerge from nozzle of nozzleassembly, and/or at a location below nozzle assembly, and may movetoward the negatively charged conduit. Using a volatile solvent, thesolution may dry substantially during transit and the fiber may bedeposited on conduit.

Material delivery assembly 305 may be fluidly attached to materialdispenser 301 via delivery tube 325. Material delivery assembly 305 mayreceive material 350 and may deliver material 350 to produce covering110 (e.g. delivers material 350 to mandrel 320 and/or conduit 120).Material delivery assembly 305 can comprise one or more pumpingmechanisms, such as a syringe pump (e.g. a syringe pump in whichmaterial 350 is contained within the syringe), a peristaltic pump, adisplacement pump and/or other pumping mechanism. Material deliveryassembly 305 can comprise linear drive assembly 345. Linear driveassembly 345 may translate nozzle 310 in at least one direction for alinear travel distance D_(SWEEP) as shown. In some cases, linear driveassembly 345 may reciprocally translate nozzle 310 along the distanceD_(SWEEP). In some cases, D_(SWEEP) may comprise a length of about 30centimeters (cm), such as a length of at least about 10 cm, about 20 cm,about 30 cm, about 35 cm, or about 40 cm. In some cases, linear driveassembly 345 may move nozzle 310 based on a construction signal 201produced by processing unit 200, such as a construction signal 201 basedon image data of conduit 120 produced by imaging device 400.

As described herein, mandrel 320 can be rotated about axis 335 duringthe delivery of material 350 by material delivery assembly 305 toproduce covering 110. In some cases, material delivery assembly 305(e.g. and nozzle 310) can rotate about mandrel 320 during delivery ofmaterial 350 (e.g. as material delivery assembly 305 and mandrel 320 maytranslate relative to each other via translational motion of either orboth).

In some cases, material 350 may comprise two or more polymers, such as afirst polymer with a first hardness, and a second polymer with a secondhardness different than the first hardness. Material 350 can comprise amixture of similar or dissimilar amounts of polyhexamethylene oxide softsegments, and aromatic methylene diphenyl isocyanate hard segments.Material 350 can comprise one or more solvents, such ashexafluoro-2-propanol (HFIP) (e.g. HFIP with an about 99.97% minimumpurity). Material 350 can comprise one or more polymers in aconcentrated solution fully or at least partially solubilized within asolvent and comprise a polymer weight to solvent volume ratio from about20% to about 35%, where a concentration may be from about 24% to about26% (more specifically from about 24.5% to about 25.5%). Material 350can comprise one or more materials with a molecular weight average (Mw)from about 80,000 to about 150,000 (polydispersity index (PDI)—molecularweight per molecular number (Mw/Mn) from about 2.1 to about 3.5).Material 350 can comprise a solution with a viscosity from about 2000centipoise (cP) to about 2400 cP (measured at about 25° C. and withshear rate equal to about 20 s⁻¹). Material 350 can comprise a solutionwith a conductivity from about 0.4 microSiemens per centimeter (μS/cm)to about 1.7 μS/cm (measured at a temperature from about 20° C. to about22° C.). Material 350 can comprise a solution with a surface tensionfrom about 21.5 milliNewtons per meter (mN/m) to about 23.0 mN/m(measured at about 25° C.).

In some cases, system 10 may be constructed and arranged to produce acovering 110 with a thickness (absent of any spine 510) of from about220 μm to about 280 μm. Covering 110 can comprise a matrix of fiberswith a diameter from about 6 μm to about 15 μm, such as a matrix offibers with an average diameter of from about 7.8 μm to about 8.6 μm.Covering 110 can comprise a porosity of from about 0% to about 99%, suchas from about 30% to about 80%, from about 40% to about 80%, or fromabout 50% to about 70%. In some cases, covering 110 may comprise anaverage compliance (“compliance” herein) from about 0.2×10⁻⁴/millimeterof mercury (mmHg) to about 3.0×10⁻⁴/mmHg when measured in arterialpressure ranges. In some cases, covering 110 may comprise an elasticmodulus from about 10 MPa to about 18 MPa.

Material delivery assembly 305 can be configured to deliver material 350to nozzle 310 at a flow rate of from about 10 milliliters per hour(ml/hr) to about 25 ml/hr, such as at a flow rate of from about 15 ml/hrto about 20 ml/hr, such as about 15 ml/hr or about 20 ml/hr.

As described above, in some cases, system 10 may be constructed andarranged to produce a graft device 100 including a spine 510. Spine 510can comprise multiple spines 510 with different inner diameters (IDs),such as multiple spines with IDs of about 4.0 millimeters (mm), about4.7 mm, and/or about 5.5 mm. Spine 510 can comprise a filament 516 witha diameter of about 0.4 mm (e.g. for a spine with an ID from about 4.0mm to about 4.7 mm). Spine 510 can comprise a filament 516 with adiameter of about 0.5 mm (e.g. for a spine with an ID from about 4.8 mmto about 5.5 mm). Spine 510 can comprise a series of inter-digitatingfingers spaced about 0.125 inches from each other so that the recurringunit of spine including one left finger and one right finger occursabout every 0.25 inches. This recurring feature length can have a rangecomprised from about 0.125 inches to about 0.375 inches. The fingers canoverlap in a symmetric or asymmetric pattern, such as an overlap ofopposing fingers from about 2.5 mm to about 1.0 mm around thecircumferential perimeter of spine 510. Spine 510 can be heat treated toachieve a resilient bias. Spine 510 can be surface-treated (e.g. withdimethylformamide) to increase the surface roughness and reducecrystallinity (e.g. to improve solvent-based adhesion with the covering110).

Spine 510 can include one or more portions that may be resilientlybiased, such as a resilient bias may be configured to provide a radialoutward force at locations proximate ends 101 and/or 102, such as toprovide a radial outward force to support or enhance the creation of ananastomosis during a cardiovascular bypass procedure. In some cases,spine 510 may include one or more portions that are malleable.

Spine 510 can include multiple curved projections 511′ and 511″,collectively 511. One or more projections 511′ (such as each projection)may include a tip portion 512′ and one or more projections 511″ (such aseach projection) may include a tip portion 512″ (collectively, tipportions 512). Tip portions 512 can be arranged in the overlappingarrangement shown in FIG. 3. Projections 511′ and 511″ can comprise afirst and second support portion, respectively, that are arranged suchthat at least one rotates relative to the other to create an opening toreceive conduit 120. In some cases, one or more tip portions 512 (suchas each tip portion) can comprise a diameter from about 0.020 inches toabout 0.064 inches, such as a diameter about 0.042 inches. One or moreprojections 511 (such as each projection) can comprise a loop of afilament (e.g. a loop of a continuous filament), and projections 511′and 511″ can be arranged in an interdigitating arrangement such as thealternating, interdigitating arrangement shown in FIG. 3. In some cases,the interdigitating projections 511′ and 511″ can overlap (e.g. spine510 covers more than 360° of conduit 120). In some cases, projections511′ and 511″ may be arranged with an overlap of at least about 1.0millimeters (mm), at least about 1.1 mm or at least about 1.4 mm. Insome cases, spine 510 can be constructed and arranged as described inapplicant's co-pending U.S. patent application Ser. No. 15/023,265,filed Mar. 18, 2016, the content of which is incorporated herein byreference in its entirety for all purposes.

A graft device can include a spine, such as to prevent luminalnarrowing, radial collapse, kinking and/or other undesired movement ofthe graft device (e.g. movement into an undesired geometricconfiguration), such as while implanting the graft device during asurgical procedure and/or at a time after implantation. The spine can beplaced inside the tubular conduit, between the tubular conduit and thefiber matrix, between layers or within layers of the fiber matrix and/oroutside the fiber matrix. The spine can comprise a biodegradable orbioerodible (hereinafter “biodegradable”) material or otherwise beconfigured to provide a temporary support to the graft device. In somecases, a spine can comprise one or more portions including durable orotherwise non-biodegradable materials configured to remain intact forlong periods of time when implanted, such as at least about 6 months orat least about 1 year.

Also provided herein are systems and methods for producing a graftdevice comprising a conduit, a surrounding fiber matrix and a spine.Systems may include an electrospinning device and/or other fiber orfiber matrix delivering assembly. In some cases, the spine may comprisea component that may be applied, placed and/or inserted, such as by thefiber matrix delivery assembly (e.g. automatically orsemi-automatically) or with a placement or insertion tool (e.g.manually).

Graft device can include spine. Spine may be constructed and arranged toprevent graft device from undergoing undesired motion such as kinking orother narrowing, such as during implantation procedure and/or whileunder stresses endured during its functional lifespan. In some cases,spine may surround conduit, positioned between conduit and fiber matrix,where spine may comprise a diameter approximating the outer diameter ofconduit. In some cases, spine, in whole or in part, can be between oneor more layers of fiber matrix. In some cases, spine, in whole or inpart, can surround fiber matrix. In some cases, spine may be positionedwithin conduit. In some cases, multiple spines can be included, eachsurrounding tubular conduit, surrounding fiber matrix and/or positionedbetween two or more layers of fiber matrix.

Spine can be constructed and arranged to provide one or more functionsselected from the group consisting of: minimizing undesirableconditions, such as buckling, conduit deformation, luminal deformation,stasis, flows characterized by significant secondary components ofvelocity vectors such as vortical, recirculating or turbulent flows,luminal collapse, and/or thrombus formation; preserving laminar flowsuch as preserving laminar flow with minimal secondary components ofvelocity, such as blood flow through graft device, blood flow proximalto graft device and/or blood flow distal to graft device; preventingbending and/or allowing proper bending of the graft device, such asbending that occurs during and/or after the implantation procedure;preventing accumulation of debris; preventing stress concentration onthe tubular wall; maintaining a defined geometry in tubular conduit;preventing axial rotation about the length of tubular conduit; andcombinations thereof. Spine and fiber matrix can comprise similarelastic moduli, such as to avoid dislocations and/or separations betweenthe two components over time, such as when graft device undergoes cyclicmotion and/or strain.

Spine can be applied around conduit prior to, during and/or afterapplication of fiber matrix to graft device. For example, spine can beapplied prior to application of fiber matrix when spine may bepositioned between conduit and fiber matrix. Spine can be applied duringapplication of fiber matrix when spine may be positioned between one ormore layers of fiber matrix. Spine can be applied after application offiber matrix when spine may be positioned outside of fiber matrix. Spinecan be applied about conduit and/or at least a layer of fiber matrixwith one or more tools.

Spine can include one or more portions that are resiliently biased, suchas a resilient bias configured to provide a radial outward force atlocations proximate ends and/or, such as to provide a radial outwardforce to support or enhance the creation of an anastomosis as describedherein. Spine can include one or more portions that are malleable.

In some cases, a spine may include multiple curved projections and,singly or collectively projections. One or more projections, such aseach projection may include a tip portion (singly or collectively, tipportions). In some cases, one or more tip portions or each tip portioncan comprise a diameter from about 0.020 inches to about 0.064 inches,such as a diameter of about 0.042 inches. One or more projections oreach projection can comprise a loop of a filament (e.g. a loop of acontinuous filament), and projections and can be arranged in aninterdigitating arrangement such as the alternating, interdigitatingarrangement. In some cases, the interdigitating projections and canoverlap (e.g. spine covers more than 360° of conduit). In some cases,projections can be arranged with an overlap of at least about 1.0 mm, atleast about 1.1 mm or at least about 1.4 mm. A set of projections cancomprise first support portion, whose tip portions can be collectivelydeflected or otherwise rotated towards the top of the page. A set ofprojections can comprise a second support portion, whose tip portionscan be collectively deflected or otherwise rotated towards the bottom ofthe page. The rotations of first support portion and second supportportion may create an opening that may allow a spine to approach andsurround conduit from the side (e.g. laterally engage conduit and/or atleast a layer of fiber matrix already applied to conduit). Rotation offirst support portion relative to second support portion and/or rotationof second support portion relative to first support portion can beperformed with one or more spine application tools.

A spine can comprise at least three projections, such as at least sixprojections. In sonic cases, a spine may include at least twoprojections for every about 15 mm of length of spine, such as at leasttwo projections for every about 7.5 mm of length of spine, or at leasttwo projections for every about 2 mm of length of spine. In some cases,spine comprises two projections for each about 6.5 mm of length ofspine.

A spine can comprise one or more continuous filaments, such as three orless continuous filaments, two or less continuous filaments, or a singlecontinuous filament. In some cases, spine may comprise a continuousfilament of at least about 15 inches long, or at least about 30 incheslong such as when spine comprises a length of about 3.5 inches. In somecases, filament may comprise a length (e.g. a continuous length or a sumof segments with a cumulative length) of about 65 inches (e.g. to createa 4.0 mm diameter spine), or a length of about 75 inches (e.g. to createa 4.7 mm diameter spine), or a length of about 85 inches (e.g. to createa 5.5 mm diameter and/or 3.5 inches long spine). A filament can comprisea relatively continuous cross section, such as an extruded or moldedfilament with a relatively continuous cross section. Spine can comprisea filament including at least a portion with a cross section with ageometry selected from the group consisting of: elliptical; circular;oval; square; rectangular; trapezoidal; parallelogram-shaped;rhomboid-shaped; T-shaped; star-shaped; spiral-shaped; (e.g. a filamentcomprising a rolled sheet); and any combination thereof. A filament cancomprise a cross section with a major axis from about 0.2 mm to about1.5 mm in length, such as a circle or oval with a major axis less thanor equal to about 1.5 mm, less than or equal to about 0.8 mm, or lessthan or equal to about 0.6 mm, or from about 0.4 mm to about 0.5 mm.Filament can comprise a cross section with a major axis greater than orequal to about 0.1 mm, such as a major axis greater than or equal toabout 0.3 mm. In sonic cases, the major axis and/or cross sectional areaof filament may be proportionally based to the diameter of spine (e.g. alarger spine diameter correlates to a larger filament diameter, such aswhen a range of different diameter spine are provided in a kit.

A spine can comprise a tubular structure, such as a full circumferential(e.g. at least) 360° or partial circumferential tubular structure. Insome cases, a spine may comprise an inner diameter D_(S) that mayapproximate the outer diameter of tubular conduit, diameter D_(TC). Insome cases, spine may comprise an inner diameter D_(S) that mayapproximate the outer diameter of a partial layer of fiber matrixcovering tubular conduit. In some cases, a spine may comprise an innerdiameter D_(S) that may approximate the outer diameter of a full layerof fiber matrix covering tubular conduit. A spine can comprise an innerdiameter of at least about 2 mm or an inner diameter of no more thanabout 20 mm. A spine can comprise a length from about 2 inches to about6 inches, such as a length from about 3 inches to about 5 inches. Insome cases, a spine may comprise multiple tubular structures withlengths from about 1 inches to about 4 inches.

A spine can comprise a material with a durometer from about 52 D toabout 120 R, such as from about 52 D to about 85 D, such as from about52 D to about 62 D. In some cases, a spine may comprise a material witha durometer of about 55 D. A spine can comprise one or more polymers,such as a polymer selected from the group consisting of: silicone;polyether block amide; polypropylene; nylon; polytetrafluoroethylene;polyethylene; ultra high molecular weight polyethylene; polycarbonates;polyolefins; polyurethanes; polyvinylchlorides; polyamides; polyimides;polyacrylates; polyphenolics; polystyrene; polycaprolactone; polylacticacid; polyglycolic acid; polyglycerol sebacate; hyaluric acid; silkfibroin collagen; elastin; poly(p-dioxanone); poly(3-hydroxybutyrate);poly(3-hydroxyvalerate); poly(valcrolactone); poly(tartronic acid);poly(beta-malonic acid); poly(propylene fumarates); a polyanhydride; atyrosine-derived polycarbonate; a polyorthoester; a degradablepolyurethane; a polyphosphazene; and any combination thereof. A spinecan comprise the same material as fiber matrix, such as when both maycomprise the same electrospun material.

A spine can comprise at least one thermoplastic co-polymer. A spine cancomprise two or more materials, such as a first material and a secondmaterial harder than the first material. In some cases, a spine cancomprise relatively equal amounts of a harder material and a softermaterial. The softer material can comprise polydimethylsiloxane and apolyether-based polyurethane and the harder material can comprisearomatic methylene diphenyl isocyanate. A spine can comprise one or moredrugs or other agents, such as one or more agents constructed andarranged to be released over time.

In some cases, a spine may comprise a metal material, such as a metalselected from the group consisting of: nickel titanium alloy; titaniumalloy; titanium; stainless steel; tantalum; magnesium; cobalt-chromiumalloy; gold; platinum; and combinations thereof. In some cases, a spinemay comprise a reinforced resin, such as a resin reinforced with carbonfiber and/or Kevlar. In some cases, at least a portion of a spine may bebiodegradable, such as when a spine may comprise a biodegradablematerial such as a biodegradable metal or biodegradable polymer. In somecases, fiber matrix can comprise a biodegradable material and/or anon-biodegradable material. In some cases, a spine may not comprise abiodegradable material. In some cases, fiber matrix can comprise abiodegradable material and/or a non-biodegradable material.

A spine can be configured to biodegrade over time such as to provide atemporary kink resistance or other function to device. In some cases, aspine can temporarily provide kink resistance to graft device for aperiod of less than about twenty-four hours. In some cases, a spine canprovide kink resistance to graft device for a period of less than aboutone month. In some cases, a spine can provide kink resistance to graftdevice for a period of less than about six months.

A spine can comprise a polymer constructed and arranged to change one ormore properties upon exposure to an external stimuli. The polymer cancomprise a polymer selected from the group consisting of:N-isopropylacrylamide (NIPAAm); a polaxamer (Pluronics); and anycombination thereof. The external stimuli can comprise a stimuliselected from the group consisting of: temperature; pH; light; magneticfield; electric field; exposure to a solvent; and any combinationthereof. The changed property can comprise a property selected from thegroup consisting of: hydrophobicity; a material property; an adhesiveproperty; size; geometry; and combinations thereof. For instance, spinecan exhibit an increase of hydrophobicity when exposed to a stimuli suchas an electromagnetic field, such as an electromagnetic field that maybe provided during an electrospinning process as described herein.

A spine can comprise one or more coatings. A coating can cover all or aportion of one or more filaments. A spine can comprise an inner surfaceand an outer surface, and coating can be positioned on inner surface, onouter surface, and/or on another surface of spine. A coating cancomprise an adhesive element or otherwise exhibit adhesive properties,such as a coating comprising a material selected from the groupconsisting of: fibrin gel; starch-based compound; mussel adhesiveprotein; and any combination thereof. A coating can be constructed andarranged to provide a function selected from the group consisting of:anti-thrombogenecity; anti-proliferation; anti-calcification;vasorelaxati on; and any combination thereof. A coating can comprise adehydrated gelatin, such as a dehydrated gelatin coating configured tohydrate to cause adherence of spine to conduit. A coating can comprise ahydrophilic and/or a hydrophobic coating. A coating can comprise aradiopaque coating. in some cases, a spine may comprise at least aportion that may be radiopaque, such as when spine may comprise aradiopaque material such as barium sulfate.

A spine can be constructed and arranged to be cut to length during themanufacturing process, such as at a time after application of at least aportion of fiber matrix. A spine can be cut with one or more tools, suchas trimming tool.

Spine 510 can comprise at least three projections 511, such as at leastsix projections 511. In some cases, spine 510 may include at least twoprojections 511 for every about 15 mm of length of spine 510, such as atleast about two projections 511 for every about 7.5 mm of length ofspine 510, or at least about two projections for every about 2 mm oflength of spine 510. In some cases, spine 510 may comprise about twoprojections 511 for each about 6.5 mm of length of spine 510. In somecases, a series of projections 511 may be positioned about 0.125 inchesfrom each other.

Spine 510 can comprise one or more continuous filaments 516, such asthree or less continuous filaments, two or less continuous filaments, ora single continuous filament. In some cases, spine 510 may comprise acontinuous filament 516 of at least about 15 inches long (i.e. thecurvilinear length), or at least about 30 inches long, such as whenspine 510 comprises a length of about 3.5 inches. In some cases,filament 516 may comprise a length (e.g. a continuous curvilinear lengthor a sum of segments with a cumulative curvilinear length) of about 65inches (e.g. to produce an about 4.0 mm diameter spine 510), or a lengthof about 75 inches (e.g. to produce an about 4.7 mm diameter spine 510),or a length of about 85 inches (e.g. to produce an about 5.5 mm diameterspine 510). Filament 516 can comprise a relatively continuous crosssection, such as an extruded or molded filament with a relativelycontinuous cross section. Spine 510 can comprise a filament 516including at least a portion with a cross sectional geometry selectedfrom the group consisting of: elliptical; circular; oval; square;rectangular; trapezoidal; parallelogram-shaped; rhomboid-shaped;T-shaped; star-shaped; spiral-shaped; (e.g. a filament comprising arolled sheet); and any combination thereof or other geometries. Filament516 can comprise a cross section with a major axis from about 0.2 mm toabout 1.5 mm in length, such as a circle or oval with a major axis lessthan or equal to about 1.5 mm, less than or equal to about 0.8 mm, orless than or equal to about 0.6 mm, or from about 0.4 mm to about 0.5mm. Filament 516 can comprise a cross section with a major axis greaterthan or equal to about 0.1 mm, such as a major axis greater than orequal to about 0.3 mm. In some cases, the major axis and/or crosssectional area of filament 516 may be proportionally based to thediameter of spine 510 (e.g. a larger spine 510 diameter may correlate toa larger filament 516 diameter, such as when a range of differentdiameter spine 510's may be provided in a kit).

Filament 516 can be a single core, monofilament structure. In somecases, filament 516 can comprise multiple filaments, such as a braidedmultiple filament structure. In some cases, filament 516 can comprise aninjection molded component or a thermoset plastic component, such aswhen spine 510 comprises multiple projections 511 that may be producedat the same time as the creation of one or more filaments 516 (e.g. whenfilament 516 may be created in a three-dimensional biased shape).

Filament 516 can comprise a 3D printed component, an extruded component,a molded component, and/or an electrospun component, such as a componentproduced by the same device used to produce covering 110 (e.g. MDD 300),such as when spine 510 and covering 110 may comprise the same or similarmaterials.

Spine 510 can comprise a material with a durometer from about 40D toabout 120R, such as from about 50D to about 85D, such as from about 52Dto about 62D. In some cases, spine 510 may comprise a material with adurometer of about 55D. Spine 510 can comprise one or more polymers,such as a polymer selected from the group consisting of: silicone;polyether block amide; polypropylene; nylon; polytetrafluoroethylene;polyethylene; ultra-high molecular weight polyethylene; polycarbonates;polyolefins; polyurethanes; polyvinylchlorides; polyamides; polyimides;polyacrylates; polyphenolics; polystyrene; polycaprolactone; polylacticacid; polyglycolic acid; polyglycerol sebacate; hyaluronic acid; silkfibroin collagen; elastin; poly(p-dioxanone); poly(3-hydroxybutyrate);poly(3-hydroxyvalerate); poly(valecrolactone); poly(tartronic acid);poly(beta-malonic acid); poly(propylene fumarates); a polyanhydride; atyrosine-derived polycarbonate; a polyorthoester; a degradablepolyurethane; a polyphosphazene; and any combination thereof or othermaterials.

Spine 510 can comprise the same or substantially similar material(s) ascovering 110. Spine 510 can comprise at least one thermoplasticco-polymer. Spine 510 can comprise two or more materials, such as afirst material and a second material harder than the first material. Insome cases, spine 510 may comprise relatively equal amounts of a hardermaterial and a softer material. The softer material can comprisepolydimethylsiloxane and a polyether-based polyurethane, and the hardermaterial can comprise aromatic methylene diphenyl isocyanate. Spine 510can comprise one or more drugs or other agents, such as one or moreagents constructed and arranged to be released over time.

In some cases, spine 510 may comprise a metal material, such as a metalselected from the group consisting of: a nickel titanium alloy; atitanium alloy; titanium; stainless steel; tantalum; magnesium;cobalt-chromium alloy; gold; platinum; and any combination thereof orother materials. In some cases, spine 510 may comprise a reinforcedresin, such as a resin reinforced with carbon fiber and/or Kevlar. Insome cases, at least a portion of spine 510 may be biodegradable, suchas when spine 510 may comprise a biodegradable material such as abiodegradable metal or biodegradable polymer. In some cases, covering110 can comprise a non-biodegradable material. In some cases, spine 510may not comprise a biodegradable material.

Spine 510 can be configured to biodegrade over time such as to provide atemporary kink resistance or other function to graft device 100. In oneembodiment, spine 510 can temporarily provide kink resistance to graftdevice 100 for a period of less than about twenty-four hours. In analternative embodiment, spine 510 can provide kink resistance to graftdevice 100 for a period of less than about one month. In yet anotherembodiment, spine 510 can provide kink resistance to graft device 100for a period of less than about six months. Numerous forms ofbiodegradable materials can be employed. Bolz et al. (U.S. Pat. No.6,287,332) discloses a biodegradable implant which may include acombination of metal materials that can be an alloy or a local galvanicelement. Metal alloys can consist of at least a first component whichforms a protecting passivation coat and a second component configured toensure sufficient corrosion of the alloy. The first component may be atleast one component selected from the group consisting of: magnesium,titanium, zirconium, niobium, tantalum, zinc and silicon, and the secondcomponent is at least one metal selected from the group consisting of:lithium, sodium, potassium, manganese, calcium and iron. Furst et al.(U.S. patent application Ser. No. 11/368,298) discloses an implantabledevice at least partially formed of a bioabsorbable metal alloy thatincludes a majority weight percent of magnesium and at least one metalselected from calcium, a rare earth metal, yttrium, zinc and/orzirconium. Doty et al. (U.S. patent application Ser. No. 11/744,977)discloses a bioabsorbable magnesium reinforced polymer stent thatincludes magnesium or magnesium alloys. Numerous biodegradable polymerscan be used such as are described herein.

System 10 can include drying assembly 650, which can be constructed andarranged to remove moisture or other fluids from conduit 120 and/orcovering 110, such as to remove solvent from locations surroundingconduit 120 and/or covering 110. Drying assembly 650 can comprise a heatgenerator, dehydrator, desiccant or other fluid absorbing material,and/or other mechanism may be configured to remove solvent fromlocations on, within, and/or proximate conduit 120 and/or covering 110.Drying assembly 650 can comprise a handheld device. In some cases,conduit 120 may comprise harvested tissue (e.g. a harvested saphenousvein segment) and drying assembly 650 may comprise gauze or othermaterial used to manually remove fluids from conduit 120, such as toremove solvents and/or improve adherence between covering 110 andconduit 120.

MDD 300 can include one or more modification assemblies constructed andarranged to modify one or more components and/or one or more portions ofgraft device 100. In the illustrated embodiment, MDD 300 may includemodification assembly 605. Modification assembly 605 may comprise anozzle assembly or other modifying element, modifying element 627.Modification assembly 605 may comprise linear drive assembly 645.Assembly 605 may be operably attached to linear drive assembly 645,which may be configured to translate assembly 605 in at least onedirection, such as a reciprocating motion in back and forth directionsspanning a distance similar to D_(SWEEP) of linear drive assembly 345.Assembly 605 can be operably attached to supply 620 via delivery tube625.

Modification assembly 605 can be configured to remove vapor from aboutconduit 120 and/or covering 110, such as to reduce the amount of solventin conduit 120 and/or covering 110. In some cases, supply 620 cancomprise a vacuum that enables modifying element 627 (e.g. a nozzle) toextract gas and/or vapor via delivery tube 625.

System 10 can include one or more graft device 100 modifying agents,such as agent 602 shown. Agent 602 can comprise a solvent configured toperform a surface modification, such as a solvent selected from thegroup consisting of: dimethylformamide; hexafluoroisopropanol;tetrahydrofuran; dimethyl sulfoxide; isopropyl alcohol; ethanol; and anycombination thereof or other solvents. In some cases, system 10 may beconstructed and arranged to perform a surface modification configured toenhance the adhesion of two or more of: conduit 120, spine 510 andcovering 110. In some cases, system 10 may be constructed and arrangedto perform a surface modification to covering 110 and/or spine 510 tocause a modification of the surface energy of covering 110 and/or spine510, respectively. In some cases, the surface of spine 510 may bemodified with a heated die comprising a textured or otherwisenon-uniform surface. In some cases, MDD 300 and/or another component ofsystem 10 may comprise a radiofrequency plasma glow discharge assemblyconstructed and arranged to perform a surface modification of spine 510,such as a process performed in the presence of a material selected fromthe group consisting of: hydrogen; nitrogen; ammonia; oxygen; carbondioxide; C2F6; C2F4; C3F6; C2H4; CH4; and any combination thereof orother materials.

Supply 620 can comprise one or more of: a reservoir of one or moreagents, such as agent 602; a power supply such as a laser power supply;and/or a reservoir of compressed fluid. In some cases, modifying element627 may comprise a nozzle, such as a nozzle configured to deliver acovering 110 modifying agent, a conduit 120 modifying agent, a spine 510modifying agent, and/or a graft device 100 modifying agent.

For clarification, any reference to a “nozzle” or “assembly”, insingular or plural form, can include one or more nozzles, such as one ormore nozzles 310 or one or more modifying elements 627 configured as anozzle, or one or more assemblies, such as one or more material deliveryassemblies 305 or one or more modification assemblies 605.

In some cases, modifying element 627 may be configured to deliver agent602. For example, agent 602 can comprise a wax, gel (e.g. a pluronic gelor other poloxamer gel) or other protective material delivered toconduit 120 prior to the application of covering 110 to conduit 120, thedelivered agent 602 may be configured to protect conduit 120 fromadverse effects of covering 110 (e.g. protection from one or moresolvents or other potentially harmful materials of covering 110). Insome cases, agent 602 can comprise a neutralizing material (e.g. amaterial configured to neutralize adverse effects of potentially harmfulmaterials), the agent 602 may be delivered to conduit 120 prior toand/or during the application of covering 110 to conduit 120. Thisdelivery of agent 602 can be performed to prevent or otherwise minimizeexposure of conduit 120 to one or more solvents (e.g.hexafluoro-2-propanol (HFIP)) may be included in material 350, and/or toreduce injury to conduit 120 by any solvent.

An agent 602 comprising a solvent-reducing material and/or a solventneutralizing material can be delivered via mandrel 320 (e.g. whenmandrel 320 comprises a porous mandrel), via modifying element 627,and/or via a separate device. Agent 602 can be applied to one or moresurfaces of conduit 120 via a method selected from the group consistingof: spraying; dipping; dripping; brushing, and any combination thereof.Agent 602 can be applied to conduit 120 prior to and/or after placingconduit 120 around mandrel 320. In some cases, agent 602 may comprise asolvent-reducing material comprising a thermogelling fluid, such aspluronic 407 poloxamer gel, or an equivalent, configured as a barrier.An agent 602 comprising a thermogel can be applied at a temperaturebelow the solution gelation temperature such that the solution is aliquid during application and gels on a surface of conduit 120. In somecases, the thermogel can be gelled prior to application onto conduit120. In some cases, an agent 602 comprising a gel or other material maybe applied at a thickness from about 0.1 mm to about 2 mm to one or moresurfaces (e.g. the entire outer surface or a portion thereof such as amajority of the outer surface) of conduit 120.

Agent 602 can comprise a thermogel solution prepared using distilled orionized water, or the thermogel can be prepared using a preservativesolution (e.g. to increase the buffering capacity of the thermogel).Examples of applicable preservative solutions may include but are notlimited to: phosphate buffered saline (PBS); cell culture media (e.g.Dulbecco's Modified Eagle Media or Gibco RPMI 1640); balanced saltsolution (e.g. lactated ringer's solution or Hank's Balanced Saltsolution); and/or a cardioplegia solution. Agent 602 can comprise one ormore materials added to a thermogel solution, such as to perform afunction selected from the group consisting of: increase bufferingcapacity of the solution; modify the pH of the solution; act as asolvent scavenger (e.g. an HFIP scavenger); and any combination thereof.For example, agent 602 can comprise: a salt (e.g. a sodium or potassiumsalt); sodium bicarbonate; powdered cell culture media; uridinediphosphate glucuronic acid; and any combination thereof. Followingapplication of covering 110 onto conduit 120, agent 602 can be left inplace during implantation of graft device 100. In some cases, graftdevice 100 can be placed in a solution (e.g. a cooled vein preservationsolution), to re-liquefy agent 602 (e.g. re-liquefy a thermogel materialcomponent of agent 602) such that it can be removed from graft device100.

Application of agent 602 (e.g. a poloxamer gel) onto a surface (e.g. theouter surface) of conduit 120 as a temporary layer between covering 110and conduit 120 may provide numerous advantages. In some cases, agent602 comprising a gel or other material can provide an adhesiveconnection between conduit 120 and covering 110, such as to improvepost-application handling of conduit 120. In some cases, agent 602 maybe applied as a temporary layer on the inner surface of conduit 120,with sufficient thickness to allow a smaller diameter mandrel 320 to beused. In some cases, trauma to conduit 120 (e.g. a vein) can be reduced.

In some cases, modifying element 627 may be configured to deliver a kinkresisting element, for example spine 510, such as a robotic assemblyconstructed and arranged to laterally deliver spine 510 about at leastconduit 120 (e.g. about conduit 120 and an inner layer of covering 110).In some cases, modifying element 627 can be configured to modify conduit120, spine 510 and/or covering 110, such as to cause graft device 100 tobe kink resistant or otherwise enhance the performance of the graftdevice 100 produced by system 10. In these graft device 100 modifyingcases, modifying element 627 can comprise a component selected from thegroup consisting of: a robotic device such as a robotic deviceconfigured to apply spine 510 to conduit 120; a nozzle, such as a nozzleconfigured to deliver agent 602; an energy delivery element, such as alaser delivery element such as a laser excimer diode or CO2 laser, oranother element configured to trim one or more components of graftdevice 100; a fluid jet, such as a water jet or air jet configured todeliver fluid during the application of covering 110 to conduit 120; acutting element, such as a cutting element configured to trim spine 510and/or covering 110; a mechanical abrader; and any combination thereofor other components. Modification of covering 110 or other graft device100 component by modifying element 627 can occur during the productionof covering 110 and/or after covering 110 has been applied to conduit120. Modification of one or more spines 510 can be performed prior toand/or after spine 510 has been applied to surround conduit 120. In somecases, modifying element 627 can be used to cut or otherwise trimcovering 110 and/or a spine 510.

In an alternative embodiment, modification assembly 605 of system 10 canbe an additional component or assembly, separate from MDD 300, such as ahandheld device configured to remove solvent and/or deliver spine 510.In some cases, modification assembly 605 may comprise a handheld laser,such as a laser device which can be hand operated by an operator. Insome cases, modification assembly 605 may comprise a fan, vacuum orother gas propelling device configured to remove solvent or otherundesired material from areas surrounding conduit 120 and/or covering110. Modification assembly 605 can be used to modify graft device 100after its removal from MDD 300, such as prior to and/or during a graftdevice 100 implantation procedure.

Laser or other modifications to covering 110 can cause portions ofcovering 110 to undergo physical changes, such as hardening, softening,melting, stiffening, creating a resilient bias, expanding, and/orcontracting, and/or can also cause covering 110 to undergo chemicalchanges, such as forming chemical bonds with an adhesive layer betweenthe outer surface of conduit 120 and covering 110 and/or a chemicalchange that reduces the amount of solvent in covering 110. In somecases, modifying element 627 may be configured to modify conduit 120,such that conduit 120 may comprise a kink resisting or other performanceenhancing element. Modifications to conduit 120 can include but are notlimited to a physical change to one or more portions of conduit 120selected from the group consisting of: drying; hardening; softening;melting; stiffening; creating a resilient bias; expanding; contracting;and any combination thereof or other changes. Modifications of conduit120 can cause conduit 120 to undergo chemical changes, such as achemical change that results in a reduction in solvent in covering 110and/or a chemical change that forms chemical bonds with an adhesivelayer between an outer surface of conduit 120 and spine 510 and/orcovering 110.

Covering 110 can include an inner layer and an outer layer. The innerlayer can include an adhesive component and/or exhibit adhesiveproperties. The inner layer can be delivered separate from the outerlayer, for example, delivered from a separate nozzle or at a separatetime during the process of creating covering 110. Selective adhesionbetween the inner and outer layers can be configured to provide kinkresistance. Spine 510 can be placed between the inner and outer layersof covering 110, such as is described herein.

In some cases, MDD 300 can be configured to deliver covering 110 and/oran adhesive layer according to set parameters configured to produce akink resistant element in and/or provide kink resisting properties tograft device 100. For example, an adhesive layer can be delivered toconduit 120 for a particular length of time, followed by delivery ofmaterial 350 for another particular length of time. An applicationparameters may include but may not be limited to: amount of adhesivelayer and/or material 350 delivered; rate of adhesive layer and/ormaterial 350 delivered; nozzle 310 distance to mandrel 320 and/orconduit 120; linear travel distance of nozzle 310 or a fiber modifyingelement 627 along its respective drive assembly (for example, lineardrive assembly 345 or 645); linear travel speed of nozzle 310 or a fibermodifying element 627 along its respective drive assembly; compositionsof material 350 and/or adhesive layer; concentrations of material 350and/or adhesive layer; solvent compositions and/or concentrations;covering 110 inner and outer layer compositions and/or concentrations;spontaneous or sequential delivery of material 350 and the adhesivelayer; flow rate of material 350 delivered to nozzle 310; pressure ofmaterial delivered to nozzle 310; temperature of nozzle 310; voltageapplied to nozzle 310; voltage applied to mandrel 320; temperature ofmandrel 320; viscosity of material 350; temperature within chamber 20;relative humidity within chamber 20; airflow within chamber 20; and anycombination thereof or other parameters.

Nozzle 310 can be constructed of stainless steel, such as passivated 304stainless steel. A volume of space surrounding nozzle 310 can bemaintained free of objects or substances which can interfere with thematerial 350 delivery process. Nozzle 310 geometry and orientation, aswell as the temperature, pressure and/or electrical potential voltages(e.g. as applied between nozzle 310 and mandrel 320) can be chosen tocontrol production of covering 110.

Mandrel 320 can be positioned in a particular spaced relationship fromassembly 305 and/or assembly 605, and nozzle 310 and/or modifyingelement 627, respectively. In the illustrated embodiment, mandrel 320may be positioned above and below assemblies 605 and 305, respectively.In some cases, mandrel 320 can be positioned above, below, to the rightand/or to the left of, assembly 305 and/or assembly 605. The distancebetween mandrel 320 and the tip of nozzle 310 and/or modifying element627 can be less than about 20 centimeter (cm), or less than about 15 cm,such as a distance of from about 12.2 cm to about 12.8 cm or about 12.5cm. In some cases, multiple nozzles 310 and/or multiple modifyingelements 627, for example components of similar or dissimilarconfigurations, can be positioned in various orientations relative tomandrel 320. In some cases, the distance between nozzles 310 and/ormodifying elements 627 and mandrel 320 may vary along the length oftheir respective travel along mandrel 320, such as to create a varyingpattern of covering 110 along conduit 120. In some cases, nozzle 310and/or modifying element 627 distances from mandrel 320 can varycontinuously during the application of material 350 and/or the distancecan vary for one or more set periods of time during the process.

In some cases, an electrical potential may be applied between nozzle 310and one or both of conduit 120 and mandrel 320 (e.g. when MDD 300 maycomprise at least an electrospinning device, such as to create at leasta portion of covering 110 and/or a spine 510). The electrical potentialcan draw at least one fiber from material delivery assembly 305 toconduit 120. Conduit 120 can act as the substrate for an electrospinningprocess, collecting the fibers that may be drawn from material deliveryassembly 305 by the electrical potential. In some cases, mandrel 320and/or conduit 120 may have a lower voltage than nozzle 310 to createthe desired electrical potential. For example, the voltage of mandrel320 and/or conduit 120 can be a negative or zero voltage while thevoltage of nozzle 310 can be a positive voltage. Mandrel 320 and/orconduit 120 can have a voltage of about −5 kiloVolts (kV) (e.g., about:−10 kV, −9 kV, −8 kV, −7 kV, −6 kV, −5 kV, −4.5 kV, −4 kV, −3.5 kV, −3.0kV, −2.5 kV, −2 kV, −1.5 kV, or −1 kV) and the nozzle 310 can have avoltage of about +15 kV (e.g., about: 2.5 kV, 5 kV, 7.5 kV, 12 kV, 13.5kV, 15 kV, 17 kV, or 20 kV). In some cases, the potential differencebetween nozzle 310 and mandrel 320 and/or conduit 120 can be from about5 kV to about 30 kV. This potential difference may draw fibers fromnozzle 310 to conduit 120. In some cases, nozzle 310 may be electricallycharged with a potential of between +15 kV and +17 kV while mandrel 320may be at a potential of about −2 kV. In some cases, mandrel 320 may bea fluid mandrel, such as the fluid mandrel described in applicant's U.S.Pat. No. 9,656,417, issued May 23, 2017, the content of which isincorporated herein by reference in its entirety for all purposes.

Mandrel 320 can be configured to rotate about an axis, such as centralaxis 335 of mandrel 320, with axis 328 of nozzle 310 may be orientedorthogonal to axis 335. In some cases, axis 328 of nozzle 310 may behorizontally offset from axis 335. The rotation around axis 335 mayallow covering 110 to be applied along all sides, or around a portion ofan entire circumference of conduit 120. In some cases, two motors 341 aand 341 b may be used to rotate mandrel 320. In some cases, MDD 300 caninclude a single motor configured to rotate mandrel 320. In some cases,mandrel 320 may not be rotated (e.g. when mandrel 320 may be a flatplate). The rate of rotation of mandrel 320 can determine how fibers maybe applied to one or more segments of conduit 120. For example, for athicker portion of covering 110, the rotation rate can be slower thanwhen a thinner portion of covering 110 is desired. In some cases,mandrel 320 may be rotated at a rate (e.g. a minimum, maximum or averagerate) of from about 100 rotations per minute (rpm) to about 500 rpm,such as a rate of from about 200 rpm to about 300 rpm, from about 240rpm to about 260 rpm, or about 250 rpm.

In addition to mandrel 320 rotating around axis 335, the materialdelivery assembly 305 can move, such as when driven by linear driveassembly 345 in a reciprocating or oscillating horizontal motion (to theleft and right of the page). Drive assembly 345, as well as linear driveassembly 645 which operably attaches to assembly 605, can individuallyor collectively comprise a linear drive assembly, such as a belt-drivenand/or gear-driven drive assembly comprising two or more pulleys drivenby one or more stepper motors. In some cases, assemblies 305 and/or 605can be constructed and arranged to rotate around axis 335, rotatingelement not shown. The length of linear drive assemblies 345 and/or 645and the linear motion applied to assemblies 305 and 605, respectively,can vary based on the length of conduit 120 to which a covering 110 isproduced and/or a covering 110 modification is applied. For example, thesupported linear motion of linear drive assemblies 345 and/or 645 cancomprise a translation distance of from about 10 centimeter (cm) toabout 50 cm, such as to cause a translation of assembly 305 and/or 605from about 27 cm to about 31 cm, or about 29 cm. Rotational speeds ofmandrel 320 and translational speeds of assemblies 305 and/or 605 can berelatively constant, or can be varied during the material 350 deliveryprocess of assembly 305 and/or modification procedure of assembly 605.In some cases, assemblies 305 and/or 605 may be translated (e.g. backand forth) at a relatively constant translation rate from about 40millimeters per second (mm/sec) to about 150 mm/sec, such as to causenozzle 310 and/or modifying element 627 to translate at a rate of fromabout 50 millimeter per second (mm/sec) to about 80 mm/sec, from about55 mm/sec to about 65 mm/sec, or about 60 mm/sec, during the majority ofits travel. In some cases, system 10 may be constructed and arranged torapidly change directions of translation (e.g. by maximizingdeceleration before a direction change and/or maximizing accelerationafter a direction change).

Assemblies 305 and/or 605 can move along the entire length and/or alongspecific portions of the length of conduit 120. In some cases, deliveryof material 350 and/or a modification may be applied to a lengthcoordinating to a portion or the entire length of conduit 120 plus anadditional about 5 cm (e.g. applied to mandrel 320). In anotherembodiment, material 350 and/or a modification may be applied to alength coordinating to a portion or the entire length of conduit 120plus at least about 1 cm. Assemblies 305 and/or 605 can be controlledsuch that specific portions along the length of conduit 120 may bereinforced with a greater amount (e.g. thicker segment) of covering 110as compared to other or remaining portions. In some cases, assemblies305 and/or 605 can be controlled such that specific portions of thelength of conduit 120 may include one or more kink resistant elements(e.g. one or more spines 510) positioned at those one or more specificconduit 120 portions. In addition, conduit 120 can be rotating aroundaxis 335 while assemblies 305 and/or 605 move, via linear driveassemblies 345 and/or 645, respectively, to position assemblies 305and/or 605 at the particular portion of conduit 120 and/or mandrel 320to which material 350 may be delivered and/or covering 110 may bemodified.

System 10 can also include a power supply, power supply 302 configuredto provide power to material delivery assembly 305 (e.g. to a pump orother fluid propulsion mechanism of material delivery assembly 305).Power supply 302 can be configured to provide electric potentials tonozzle 310 and mandrel 320, and/or to supply power to other componentsof system 10 such as linear drive assemblies 345 and 645 and assembly605. Power supply 302 can be connected, either directly or indirectly,to at least one of mandrel 320 or conduit 120. Power can be transferredfrom power supply 302 to one or more components (such as each component)by, for example, one or more wires.

System 10 can include an environmental control assembly includingenvironmental chamber, chamber 20, that may surround MDD 300 (e.g. atleast during the creation of covering 110). System 10 can be constructedand arranged to control the environmental conditions within chamber 20,such as to control one or more areas surrounding material deliveryassembly 305 and/or mandrel 320 during the application of covering 110to conduit 120. Chamber 20 can include inlet port assembly 21 and outletport assembly 22. Inlet port assembly 21 and/or outlet port assembly 22can include one or more components such as one or more componentsselected from the group consisting of: a fan; a source of a gas such asa dry compressed air source; a source of gas at a negative pressure; avapor source such as a source including a buffered vapor, an alkalinevapor and/or an acidic vapor; a filter such as a high efficiencyparticulate air (HEPA) filter; a dehumidifier; a humidifier; a heater; achiller; and electrostatic discharge reducing ion generator; and anycombination thereof. Chamber 20 can include one or more environmentalcontrol components that can monitor and/or control temperature, humidityand/or pressure within chamber 20 (e.g. one or more environmentalcontrol components controlled by environmental controller 35). Chamber20 can be constructed and arranged to provide relatively uniformventilation about mandrel 320 (e.g. about conduit 120, covering 110and/or spine 510) including an ultra-dry (e.g. ≤about 2 part per million(ppm) water or other liquid content) compressed gas (e.g. air) sourcemay be configured to reduce humidity within chamber 20. Inlet portassembly 21 and outlet port assembly 22 can be oriented to purge airfrom the top of chamber 20 to the bottom of chamber 20 (e.g. to removevapors of one or more solvents such as hexafluoro-2-propanol (HFIP),which can tend to settle at the bottom of chamber 20). Chamber 20 can beconstructed and arranged to replace the internal volume of chamber 20 atleast once every about 3 minutes, or once every about 1 minute, or onceevery about 30 seconds. Outlet port assembly 22 can include one or morefilters 24 (e.g. replaceable cartridge filters) which may be suitablefor retaining solvent or other potentially harmful components ofmaterial 350 (e.g. by filtering vapor including solvent) or to retainother undesired materials evacuated from chamber 20. In some cases,inlet port assembly 21 can include one or more filters 23 which aresimilarly suitable for retaining solvent or other undesired materialsdelivered into chamber 20. Chamber 20 can be constructed and arranged tomaintain a flow rate through chamber 20 of at least about 30 liters perminute (L/min), such as at least about 45 L/min or at least about 60L/min, such as during an initial purge procedure. Subsequent to aninitial purge procedure, a flow rate of at least about 5 L/min, at leastabout 10 L/min, at least about 20 L/min or at least about 30 L/min canbe maintained, such as to maintain a constant humidity level (e.g. arelative humidity from about 20% to about 24%). Chamber 20 can beconstructed and arranged to control temperature, such as to controltemperature within chamber 20 to a temperature from about 15° C. toabout 25° C., such as from about 16° C. to about 20° C. with a relativehumidity from about 20% to about 24%. In some cases, one or more objectsor surfaces within chamber 20 may be constructed of an electricallyinsulating material and/or may not include sharp edges or exposedelectrical components. In some cases, one or more metal objects may bepositioned within chamber 20 and may be electrically grounded and/ormaintained at a particular desired voltage level (e.g. a voltage leveldifferent than the voltage level of nozzle 310 and/or different than thevoltage level of mandrel 320).

In some cases, system 10 may be configured to produce a first graftdevice, graft device 100′ based on one or more component or processparameters. In some cases, graft device 100′ may comprise conduit 120′and a covering 110′ applied by MDD 300 (e.g. a 3D printer or otherlayered deposition device). Covering 110′ can be produced by materialdelivery assembly 305 supplied with material 350, such as at a flow rateof about 15 milliliter per hour (ml/hr). Cumulative application time ofcovering 110′ can comprise an approximate time period of from about 11minutes and 40 seconds to about 17 minutes and 30 seconds. Thecumulative application time of covering 110′ can comprise a time periodof from about 11 minutes and 40 seconds when conduit 120′ may comprisean outer diameter of from about 3.4 millimeter (mm) to about 4.2 mm, atime period of about 14 minutes and 0 seconds when conduit 120′ maycomprise an outer diameter from about 4.2 mm to about 5.1 mm, and/or atime period of about 17 minutes and 30 seconds when conduit 120′ maycomprise an outer diameter from about 5.1 mm to about 6.0 mm.

Covering 110′ can comprise an average fiber size of about 7.8 micrometer(μm), such as a population of fiber diameters with an average fiber sizeof about 7.8 μm with a standard deviation of about 0.45 μm. Covering110′ can comprise an average porosity of about 50.4%, such as a range ofporosities with an average of about 50.4% and a standard deviation ofabout 1.1%. Covering 110′ can comprise a strength property selected fromthe group consisting of: stress measured at about 5% strain comprising alevel from about 0.4 megapascal (MPa) to about 1.1 MPa; ultimate stressat a level of from about 4.5 MPa to about 7.0 MPa; ultimate strain at alevel of from about 200% to about 400%; and any combination thereof.Covering 110′ can comprise a compliance from about 0.2×10⁻⁴/mmHg toabout 3.0×10⁻⁴/mmHg when measured in arterial pressure ranges. Covering110′ can comprise an elastic modulus from about 10 MPa to about 15 MPa.Covering 110′ can be constructed and arranged with a targeted sutureretention strength, such as an approximate suture retention strength offrom about 2.0 Newton (N) to about 4.0 N with 6-0 Prolene® suture (orequivalent) and/or from about 1.5 N to about 3.0 N with 7-0 Prolene®suture (or equivalent). In some cases, graft device 100′ may include aspine 510′, such as a spine 510′ placed between inner and outer layersof covering 110′ (e.g. placed after one-third of the total thickness ofcovering 110′ may be applied about conduit 120′ or otherwise produced).

In some cases, system 10 may be configured to produce a second graftdevice, graft device 100″ based on one or more component or processparameters. In some cases, graft device 100″ may comprise conduit 120″and a covering 110″ produced by MDD 300. Covering 110″ can be appliedvia material delivery assembly 305 supplied with material 350 at a flowrate of about 20 milliliter per hour (ml/hr). Cumulative applicationtime of covering 110″ can comprise an approximate time period of fromabout 9 minutes and 30 seconds to about 13 minutes and 40 seconds. Thecumulative application time of covering 110″ can comprise a time periodof about 9 minutes and 30 seconds when conduit 120″ may comprise anouter diameter from about 3.4 millimeters (mm) to about 4.2 mm; a timeperiod of about 11 minutes and 30 seconds when conduit 120″ may comprisean outer diameter from about 4.2 mm to about 5.1 mm, and/or a timeperiod of about 13 minutes and 40 seconds when conduit 120″ may comprisean outer diameter from about 5.2 mm to about 6.0 mm.

Covering 110″ can comprise an average fiber size of about 8.6 micrometer(μm), such as a population of fiber diameters with an average fiber sizeof about 8.6 μm with a standard deviation of about 0.45 μm. Covering110″ can comprise an average porosity of about 46.9%, such as a range ofporosities with an average of about 46.9% and a standard deviation ofabout 0.9%. Covering 110″ can comprise a strength property selected fromthe group consisting of: stress at about 5% strain comprising a levelfrom about 0.6 MPa to about 1.3 MPa; ultimate stress at a level of fromabout 5.0 MPa to about 7.5 MPa; ultimate strain at a level of from about200% to about 400%; and any combination thereof. Covering 110″ cancomprise a compliance from about 0.2×10⁻⁴/mmHg to about 3.0×10⁻⁴/mmHgwhen measured in arterial pressure ranges. Covering 110″ can comprise anelastic modulus from about 12 MPa to about 18 MPa. Covering 110″ can beconstructed and arranged with a targeted suture retention strength, suchas an approximate suture retention strength of from about 2.3 Newton (N)to about 4.3 N with 6-0 Prolene® suture and/or from about 2.0 N to about3.5 N with 7-0 Prolene® suture. In some cases, graft device 100″ mayinclude a spine 510″, such as a spine 510″ placed between inner andouter layers of covering 110″ (e.g. placed after one-third of the totalthickness of covering 110″ may be applied about conduit 120″ orotherwise produced).

Coverings 110′ and 110″ can comprise one or more similar features and/orone or more dissimilar features. Covering 110″ of graft device 100″ cancomprise more bonds between fibers than covering 110′ of graft device100′. The increased number of bonds can result in a higher covering 110″density which can be configured to limit cellular infiltration intograft device 100″ (e.g. to increase the graft durability in vivo).Covering 110″ can comprise fibers that are flatter (i.e. more ovalversus round) and/or denser than fibers of covering 110′. Covering 110″can have a greater resiliency than covering 110′.

System 10 can comprise one or more solvent-reducing materials, such assolvent-reducing material 640 shown positioned within supply 620. Insome cases, modification assembly 605 may be configured to deliversolvent-reducing material 640 to conduit 120 and/or covering 110 (e.g.onto conduit 120 and/or covering 110). In some cases, solvent-reducingmaterial 640 may comprise a material selected from the group consistingof: a desiccant; a material configured to bond with solvent; a materialconfigured to absorb solvent; a neutralizing agent configured toneutralize solvent (e.g. make less toxic or otherwise less harmful tothe patient); and any combination thereof. In some cases,solvent-reducing material 640 may be delivered onto conduit 120 tocreate a barrier (e.g. a barrier layer) between conduit 120 and anapplied layer of covering 110 comprising solvent. In some cases,solvent-reducing material 640 may comprise a material selected from thegroup consisting of: desiccant; lipid; phospholipid; buffer; pH buffer;polyethylene; polytetrafluoroethylene (PTFE); fibrin; albumin; gelatin;oil; wax; polyethylene glycol (PEG); carbon particle; activated carbonparticle; alkaline material; powder; carbon particles; polymer beads;polymer gel; wicking fibrous membrane; solvent capillary transportsystem; ionizing gas; plasma; and any combination thereof. In somecases, solvent-reducing material 640 may comprise a pH buffer and/oralkaline material configured to prevent undesired pH changes in conduit120. In some cases, solvent-reducing material 640 may comprise anionizing gas configured to absorb or otherwise neutralize solvent. Forexample, a “cloud” of ionizing gas may be positioned proximate theconduit 120 such that material delivered by material delivery assembly305 pass through the ionizing gas and attenuate the negative effects ofsolvent.

In some cases, solvent-reducing material 640 may comprise a materialpositioned as a barrier between conduit 120 and covering 110. In somecases, solvent-reducing material 640 may comprise a removable orotherwise temporary barrier (e.g. a barrier removed prior toimplantation of graft device 100 in the patient). In some cases,solvent-reducing material 640 may be applied to a surface of the conduit120 and/or covering 110 (e.g. an inner layer of the covering 110). Insome cases, solvent-reducing material 640 may be delivered to conduit120 and/or covering 110 during application of material by materialdelivery assembly 305. In some cases, solvent-reducing material 640 maycomprise a material configured to neutralize solvent, such asneutralizing agent 641 described herein.

System 10 can comprise one or more solvent neutralizing materials, suchas solvent neutralizing material 641 shown positioned within supply 620.Solvent neutralizing material 641 can comprise a material configured toreduce injury to conduit 120 by solvent (e.g. when conduit 120 comprisesa vein segment or other living tissue). In some cases, modificationassembly 605 may be configured to deliver solvent neutralizing material641 to conduit 120 and/or covering 110 (e.g. onto conduit 120 and/orcovering 110), such as an application that may occur prior to thedelivery of covering 110, during the delivery of covering 110 (e.g.delivered while material 350 may be delivered, or delivered to a partiallayer of covering 110 when no material 350 may be applied) and/or afterthe delivery of covering 110. In some cases, solvent neutralizingmaterial 641 may comprise a material selected from the group consistingof: a buffer; polyethylene; polytetrafluoroethylene (PTFE); fibrin;albumin; gelatin; polyethylene glycol (PEG); carbon particle; activatedcarbon particle; sulfate; phosphate; ADP; ATP converted from ADP; anacid reducing material; a lipid; a phospholipid; an acidophilicbacteria; an alkaliphilic bacteria; and any combination thereof. In somecases, solvent neutralizing material 641 may be positioned about atleast a portion of conduit 120 and/or an inner layer of covering 110 tofunction as a barrier to prevent interaction between solvent and conduit120. In some cases, the barrier can be configured to be removable (e.g.dissolvable or otherwise removable) prior to implantation of graftdevice 100 in the patient. In some cases, solvent neutralizing material641 (and the resultant barrier) can comprise a material selected fromthe group consisting of: lipid; phospholipid; buffer; pH buffer;polyethylene; PTFE; fibrin; albumin; gelatin; oil; wax; PEG; carbonparticle; activated carbon particle; alkaline material; powder; carbonparticles; polymer beads; polymer gel; and any combination thereof.

System 10 can comprise one or more solvent-reducing elements, such assolvent-reducing element 40 and/or solvent-reducing element 361 of FIG.3. Solvent-reducing element 40, shown positioned in chamber 20, andsolvent-reducing element 361, shown positioned in NIDD 300, can compriseone or more devices or components configured to extract solvent, such asto extract solvent from conduit 120 (e.g. from the wall of conduit 120),from covering 110 (e.g. from one or more layers of covering 110), and/orfrom locations surrounding these (e.g. one or more locations withinchamber 20). Solvent-reducing element 40 and/or 361 can comprise acomponent selected from the group consisting of: fan; nozzle; filter;electrostatic filter; osmotic membrane; fluid delivery element; fluidextraction element; vacuum applying element; agitating element; heatingelement; cooling element; sponge; diffusion enhancing element;desiccant; forced convection element; and any combination thereof. Insome cases, solvent-reducing element 40 and/or 361 can comprise asolvent-reducing material (e.g. a material configured to reduce solventor other undesired substance), such as a material selected from thegroup consisting of: a desiccant; a material configured to bond withsolvent; a material configured to absorb solvent; a material configuredto neutralize solvent (e.g. make less toxic or otherwise less harmful tothe patient); and any combination thereof.

In some cases, solvent-reducing element 40 and/or 361 may comprise afluid extraction element configured to reduce solvent, such as a vacuumapplying element. In some cases, nozzle 310 and/or modifying element 627can comprise the solvent-reducing element configured to extract fluidand/or apply a vacuum. In some cases, solvent-reducing element 40 and/or361 may comprise a temperature control element configured to reducesolvent, such as when environmental controller 35 may adjust or mayotherwise control the temperature within chamber 20 to cause a reductionin solvent. In some cases, solvent-reducing element 40 and/or 361 maycomprise a fluid delivery element configured to deliver a gas or otherfluid proximate conduit 120 to remove solvent (e.g. when nozzle 310and/or modifying element 627 comprise the solvent-reducing elementdelivering the fluid to enhance diffusion of solvent). In some cases,solvent-reducing element 40 and/or 361 comprise an agitating element,such as a fan or other agitating element proximate conduit 120 (e.g. tocreate a stream of laminar or turbulent gas flow proximate conduit 120).In some cases, solvent-reducing element 40 and/or 361 may comprise ahumidity control element configured to remove solvent. In some cases,solvent-reducing element 40 and/or 361 may comprise at least areplaceable portion (e.g. a disposable portion used on a single patientonly). In some cases, solvent-reducing element 40 and/or 361 maycomprise a translatable element, such as when nozzle 310 and/ormodifying element 627 may comprise the solvent-reducing element and maybe translated by linear drive assemblies 345 and/or 645, respectively.In some cases, solvent-reducing element 40 and/or 361 may comprise oneor more elements configured to rotate and/or translate relative toconduit 120.

System 10 can comprise one or more sensors, such as one or more sensorsconfigured to detect the presence or level of one or more solvents (e.g.sensors that produce a signal related to a solvent level). In somecases, chamber 20 may comprise sensor 26 comprising one or more sensors.In some cases, controller 30 may comprise sensor 36 comprising one ormore sensors. In some cases, mandrel 320 may comprise sensor 329comprising one or more sensors (e.g. a sensor configured to measure aparameter of conduit 120 such as a level of solvent). In some cases,material delivery assembly 305 may comprise sensor 309 comprising one ormore sensors. In some cases, MDD 300 may comprise sensor 369 comprisingone or more sensors. In some cases, modification assembly 605 maycomprise sensor 606 comprising one or more sensors. Sensor 26, 36, 329,309, 369 and/or 606 can individually or any combination thereof compriseone or more sensors configured to measure a parameter (e.g. configuredto produce a signal related to the level of a solvent) and may produce asignal based on the measured parameter. In some cases, sensor 26, 36,329, 309, 369 and/or 606 can be configured to measure the concentrationor other amount of solvent present within conduit 120 (e.g. within awall of conduit 120), covering 110 and/or a location within chamber 20.System 10 can be configured to adjust one or more system parametersbased on the sensor signal produced by sensor 26, 36, 329, 309, 369and/or 606. In some cases, system 10 can be configured to alert anoperator that the level of solvent present in graft device 100 may bebelow a threshold (e.g. to indicate that graft device 100 may be readyfor implantation based on a measured level of solvent detected).

In some cases, sensor 26, 36, 329, 309, 369 and/or 606 comprise one ormore sensors selected from the group consisting of: optical sensor;temperature sensor; humidity sensor; pH sensor; ganged litmus paperinstrument; strain gauge; accelerometer; load cell; electrochemicalsensor; pressure sensor; chemical sensor; a color changing chemicalsensor; a photoionization sensor; fluorine sensor; a temperature sensorconfigured to measure cooling of the conduit 120 (e.g. to assessevacuation of solvent); one or more temperature sensors configured tomeasure the temperature difference between inlet port assembly 21 andoutlet port assembly 22; a sensor configured to measure the weight of atleast a portion of graft device 100; a sensor configured to measure themass of at least a portion of graft device 100; a sensor configured tomeasure the acidity of at least a portion of graft device 100; a sensorconfigured to measure a parameter of the exhaust of chamber 20 (e.g.exhaust through outlet port assembly 22); and any combination thereof.System 10 can be configured to adjust one or more system parametersbased on the one or more signals produced by one or more sensors 26, 36,329, 309, 369 and/or 606. The one or more system parameters adjusted cancomprise one or more parameters selected from the group consisting of:temperature proximate the conduit 120; flow rate of fluid proximate theconduit 120; rotation rate of the conduit 120; translation rate of theconduit 120; rotation rate of material delivery assembly 305;translation rate of the material delivery assembly 305; a nozzle 310 toa mandrel 320 distance; and any combination thereof. The one or moresystem parameters can be adjusted prior to, during and/or after deliveryof covering 110 to conduit 120.

In some cases, sensor 26, 36, 329, 309, 369 and/or 606 may comprise oneor more sensors configured to produce a signal representing a solventparameter level (e.g. a solvent concentration or other quantitativeassessment of the presence of solvent). System 10 can be configured toreduce solvent until the solvent parameter level reaches a threshold(e.g. falls below a maximum level). For example, system 10 can beconfigured to perform a function selected from the group consisting of:maintaining graft device 100 within chamber 20 (e.g. maintaining graftdevice 100 within chamber 20 in a sterile condition and/or undercontrolled environmental conditions); rotating the graft device 100(e.g. rotating conduit 120 and at least a portion of covering 110);providing a flow of gas proximate the graft device 100; providing anelevated temperature proximate the graft device 100; providing adesiccant proximate the graft device 100; and any combination thereof.

In some cases, material delivery assembly 305 may be configured todeliver fibers with an aspect ratio above 1 and/or to deliver hollowfibers, such that solvent more rapidly evacuates the fiber. In somecases, material delivery assembly 305 may be configured to deliverfibers with an aspect ratio from about 1.01:1 to about 10:1.

In some cases, system 10 may comprise one or more functional elements,such as functional element 25 shown positioned on chamber 20. Functionalelement 25 can comprise an element configured to remove solvent and/orto reduce the effects of solvent on conduit 120 (e.g. a vein segment orother living tissue). In some cases, functional element 25 may comprisean element selected from the group consisting of: fan; nozzle; filter;electrostatic filter; osmotic membrane; fluid delivery element; fluidextraction element; vacuum applying element; agitating element; heatingelement; cooling element; sponge; diffusion enhancing element;desiccant; forced convection element; and any combination thereof. Insome cases, functional element 25 may comprise one or more elementspositioned in MDD 300 or another component of system 10.

In some cases, system 10 may be configured to reduce solvent by rotatingthe conduit 120. For example, system 10 can be configured to perform arotation with or without the simultaneous delivery of fibers to conduit120, such as by rotating at an increased rotational velocity duringdelivery of fibers, and/or a rotation that may occur while no fibers maybe delivered by material delivery assembly 305 (e.g. a rotation afterdelivery of covering 110 may be complete). In some cases, system 10 maybe configured to rotate conduit 120 and/or covering 110 at a minimumvelocity (e.g. a constant or variable rate that may include a rategreater than about 250 rotations per minute (rpm)) for a minimum timeperiod (e.g. longer than about 1 second), in order to sufficientlyreduce the amount of solvent present in graft device 100. In some cases,system 10 may be configured to rotate covering 110 at a first rate whilecovering 110 may be being delivered by material delivery assembly 305,and to rotate covering 110 at a second rate (e.g. a higher rate) afterthe delivery of covering 110 may be completed.

While conduit 120 may be described in relation to a hollow, tubularstructure, any geometry may be considered within the scope of thepresent disclosure, including both non-hollow and/or non-tubularstructures. Similarly, while device 100 may be described in terms of agraft device or other device configured to fluidly connect two or moreanatomical locations (e.g. two or more blood vessels), graft device 100can comprise any type of implant for a patient. In some cases, graftdevice 100 may be configured as an implant used to replace, augment orotherwise treat cartilage, ligament, bone, a disc, soft tissue and/orother tissue of the patient.

The foregoing description and accompanying drawings set forth a numberof examples of representative embodiments at the present time. Variousmodifications, additions and alternative designs may become apparent tothose skilled in the art in light of the foregoing teachings withoutdeparting from the spirit hereof, or exceeding the scope hereof, whichis indicated by the following claims rather than by the foregoingdescription. All changes and variations that fall within the meaning andrange of equivalency of the claims are to be embraced within theirscope.

What is claimed is:
 1. System for producing a graft device for a patient comprising: an imaging device configured to produce image data of a tubular conduit; and a processing unit configured to receive the image data from the imaging device and comprising an algorithm, wherein the algorithm is configured to process the image data and produce a construction signal based on the image data; a material delivery device configured to receive the construction signal from the processing unit, and deliver material to produce a 3-dimensional (3D) covering based on the construction signal; wherein the graft device comprises the 3D covering positioned about the tubular conduit.
 2. The system according to any claim herein, wherein the material delivery device is configured to deliver the 3D covering onto the tubular conduit.
 3. The system according to any claim herein, wherein the 3D covering is configured to be positioned about the tubular conduit after being produced by the material delivery device.
 4. The system according to any claim herein, wherein the graft device comprises a coronary artery bypass graft.
 5. The system according to any claim herein, wherein the graft device comprises a dialysis graft.
 6. The system according to any claim herein, wherein the graft device comprises an implant selected from the group consisting of: artery bypass graft; coronary artery bypass graft; dialysis graft; peripheral arterial bypass graft; great vessel replacement; great vessel bypass graft; esophageal graft; tracheal graft; bronchial graft; biliary duct graft; intestinal graft; organ transplant vascular connection graft; neuronal replacement implant; ligament graft; ligament replacement; tendon graft; tendon replacement; transplant organ coating; fallopian tube; urethra; ureter; cartilage; hip joint; shoulder joint; intervertebral disc; menisci; and any combination thereof.
 7. The system according to any claim herein, wherein the imaging device comprises a device selected from the group consisting of: computerized tomography (CT) imager; optical coherence tomography (OCT) imager; magnetic resonance imaging (MRI); 3D Scanner; Camera; Infrared Camera; Ultrasound imager; and any combination thereof.
 8. The system according to any claim herein, wherein the image data comprises information related to the tubular conduit.
 9. The system according to any claim herein, wherein the image data comprises information related to a portion of the patient's anatomy.
 10. The system according to any claim herein, wherein the image data comprises data collected when the tubular conduit is in-situ.
 11. The system according to claim 10, wherein the image data further comprises data collected after the tubular conduit is harvested from the patient.
 12. The system according to any claim herein, wherein the image data comprises data collected after the tubular conduit is harvested from the patient.
 13. The system according to any claim herein, wherein the image data comprises data selected from the group consisting of: surface topography data; surface geometry data; periphery data; length data; diameter data; thickness data such as wall thickness data; taper data; eccentricity data; relative position data; trajectory data; speed of motion data; relative angle data; radiopacity data; blood flow data; echographic data; spectroscopic data; and any combination thereof.
 14. The system according to any claim herein, wherein the image data comprises at least one discrete feature of the tubular conduit.
 15. The system according to claim 14, wherein the at least one discrete feature is identified by the algorithm.
 16. The system according to claim 14, wherein the at least one discrete feature comprises a feature selected from the group consisting of: sidebranch; recess; projection; end; end portion; bend portion; lobe; bifurcation; trifurcation; a dilated portion; a swollen portion; valve; a tapered portion; a location of a surgical staple; an angled portion; a calcified tissue portion; an atheromatous tissue portion; a partially occluded portion; a fully occluded portion; and any combination thereof.
 17. The system according to claim 14, wherein the at least one discrete feature comprises a sidebranch.
 18. The system according to claim 17, wherein the image data comprises sidebranch information selected from the group consisting of: location; diameter; taper angle; ligation device position; ligation device geometry; ligation device type; and any combination thereof.
 19. The system according to any claim herein, wherein the image data comprises information related to a compliance of the tubular conduit.
 20. The system according to any claim herein, wherein the image data comprises information related to a shape of the tubular conduit changing over time.
 21. The system according to claim 20, wherein the information related to the shape of the tubular conduit changing over time comprises information related to the shape of the tubular conduit changing over time prior to harvesting.
 22. The system according to claim 20, wherein the tubular conduit changes shape due to a change in a parameter selected from the group consisting of: blood pressure; respiration; patient movement; and any combination thereof.
 23. The system according to any claim herein, wherein the tubular conduit comprises tissue selected from the group consisting of: cylindrical tissue; organ tissue; saphenous vein; vein; artery; urethra; intestine; esophagus; ureter; trachea; bronchi; duct; fallopian tube; and any combination thereof.
 24. The system according to any claim herein, wherein the tubular conduit comprises tissue selected from the group consisting of: bone; ligament; tendon; and any combination thereof.
 25. The system according to any claim herein, wherein the tubular conduit comprises artificial material.
 26. The system according to any claim herein, wherein the processing unit comprises memory circuitry.
 27. The system according to claim 26, wherein the memory circuitry is configured to store information selected from the group consisting of: tissue type; type of the material; information regarding the application of the graft device; information regarding use of one or more tools; compliance information; density information; strength information; modulus of elasticity information; elastic limit information; wall thickness information; shrinkage information of the material; cure time information of the material; spacing to a mandrel and/or other target; minimum bend radius of the covering; maximum ovality of the covering; and any combination thereof.
 28. The system according to claim 26, wherein the construction signal is based on information stored in the memory circuitry.
 29. The system according to any claim herein, wherein the processing unit comprises at least one of a microprocessor or a microcontroller.
 30. The system according to any claim herein, wherein the algorithm is configured to identify at least one discrete feature of the tubular conduit.
 31. The system according to claim 30, wherein the at least one discrete feature of the tubular conduit identified by the algorithm comprises a feature selected from the group consisting of: sidebranch; recess; projection; end; end portion; bend portion; lobe; bifurcation; trifurcation; a dilated portion; a swollen portion; valve; a tapered portion; a location of a surgical staple; an angled portion; a calcified tissue portion; an atheromatous tissue portion; a partially occluded portion; a fully occluded portion; and any combination thereof.
 32. The system according to claim 30, wherein the 3D covering comprises at least one customized portion positioned relative to the at least one discrete feature.
 33. The system according to claim 32, wherein the customized portion is positioned proximate the at least one discrete feature.
 34. The system according to claim 32, wherein the algorithm is configured to identify at least two discrete features of the tubular conduit, and wherein the 3D covering comprises at least two customized portions.
 35. The system according to claim 32, wherein the customized portion comprises a differentiating property selected from the group consisting of: different thickness; different material; different porosity; different pore size; different compliance in one or more directions; different level of conformality; different texture; different alignment and/or orientation of the deposited material; different stiffness; different fiber diameter; addition of a kink-resisting element; addition of an agent; and any combination thereof.
 36. The system according to claim 31, wherein the at least one discrete feature comprises a protrusion of the tubular conduit.
 37. The system according to claim 36, wherein the protrusion comprises a sidebranch.
 38. The system according to claim 36, wherein the 3D covering comprises a customized portion including a void proximate the protrusion.
 39. The system according to claim 38, wherein the void comprises a hole.
 40. The system according to claim 38, wherein the void comprises a recess.
 41. The system according to claim 36, wherein the at least one customized portion comprises a portion selected from the group consisting of: a portion comprising a change in deposition of the material such as to mechanically reinforce and/or provide a strain relief at a sidebranch location; a portion configured to constrain a sidebranch such as to minimize hemodynamic disruption in a lumen of the tubular conduit; and any combination thereof.
 42. The system according to claim 31, wherein the 3D covering comprises a customized portion including a fillet positioned proximate the at least one discrete feature.
 43. The system according to claim 31, wherein the at least one discrete feature comprises an end of the tubular conduit.
 44. The system according to claim 43, wherein the 3D covering comprises a customized portion including a taper located proximate the end of the tubular conduit.
 45. The system according to claim 44, wherein the at least one discrete feature further comprises a second end of the tubular conduit, and wherein the 3D covering further comprises a second customized portion including a second tapered positioned proximate the second end of the tubular conduit.
 46. The system according to claim 43, wherein the 3D covering comprises a customized portion including a reinforced portion located proximate the end of the tubular conduit.
 47. The system according to claim 43, wherein the 3D covering comprises a customized portion including an optimized anastomosis portion located proximate the end of the tubular conduit.
 48. The system according to claim 47, wherein the optimized anastomosis portion comprises an optimized shape.
 49. The system according to claim 47, wherein the optimized anastomosis portion comprises an optimized structure.
 50. The system according to claim 31, wherein the at least one discrete feature comprises tissue whose softness is above a threshold.
 51. The system according to claim 50, wherein the customized portion comprises a differentiating property selected from the group consisting of: different material; different compliance; different thickness; different permeability; different porosity; different anisotropy; and any combination thereof.
 52. The system according to claim 31, wherein the at least one discrete feature comprises tissue whose flexibility is above a threshold.
 53. The system according to claim 52, wherein the customized portion comprises a differentiating property selected from the group consisting of: different material; different compliance; different thickness; different permeability; different porosity; different anisotropy; and any combination thereof.
 54. The system according to claim 31, wherein the at least one discrete feature comprises tissue whose shape changes over time.
 55. The system according to claim 54, wherein the customized portion comprises a differentiating property selected from the group consisting of: different material; different compliance; different thickness; different permeability; different porosity; different anisotropy; and any combination thereof.
 56. The system according to claim 31, wherein the 3D covering includes a customized portion including a reinforced portion.
 57. The system according to claim 56, wherein the at least one discrete feature comprises a thin-walled portion of the tubular conduit, and wherein the customized portion is located proximate the thin-walled portion.
 58. The system according to claim 31, wherein the 3D covering includes a customized portion including a strain relief.
 59. The system according to claim 58, wherein the at least one discrete feature comprises at least one of an end of the tubular conduit or a bend portion of the graft device, and wherein the customized portion is located proximate the at least one discrete feature.
 60. The system according to claim 31, wherein the 3D covering includes a customized portion including modified porosity.
 61. The system according to claim 60, wherein the at least one discrete feature comprises an anastomosis site and/or a segment of high curvature of the graft device, and wherein the customized portion is located proximate the at least one discrete feature.
 62. The system according to claim 31, wherein the 3D covering includes a customized portion including a modified compliance.
 63. The system according to claim 62, wherein the modified compliance comprises a modified radial compliance.
 64. The system according to claim 62, wherein the modified compliance comprises a modified axial compliance.
 65. The system according to claim 62, wherein the at least one discrete feature comprises an anastomosis site, a ligament attachment site, a tendon attachment site and/or a site of segmented compliance, and wherein the customized portion is located proximate the at least one discrete feature.
 66. The system according to any claim herein, wherein the algorithm is configured to create a 3D model of the tubular conduit based on the image data.
 67. The system according to claim 66, wherein 3D model comprises a spatial model.
 68. The system according to claim 66, wherein the algorithm is further configured to modify the 3D model of the tubular conduit.
 69. The system according to claim 66, wherein the image data comprises multiple slices of a CT image.
 70. The system according to any claim herein, wherein the algorithm is configured to create a 3D model of a proposed 3D cover.
 71. The system according to any claim herein, wherein the algorithm is configured to create a proposed 3D model of the 3D covering, and to modify the proposed 3D model to create a final 3D model of the 3D covering.
 72. The system according to claim 71, wherein the algorithm is configured to modify the proposed 3D model based on at least one discrete feature of the tubular conduit.
 73. The system according to claim 71, wherein the algorithm is configured to modify the proposed 3D model based on user input.
 74. The system according to any claim herein, wherein the algorithm is configured to create a 3D model of at least one of the tubular conduit or the 3D covering based on boundary conditions.
 75. The system according to claim 74, wherein the algorithm is configured to optimize hemodynamics within the tubular conduit by performing a function selected from the group consisting of: reducing flow turbulence; controlling bending radius; controlling lumen geometry; controlling a transition; controlling a taper; controlling a bend portion; controlling tortuosity; controlling wall shear; preventing buckling; optimizing wall shear stress; modifying an end portion to optimize an anastomotic connection; reducing geometric mismatch near an anastomotic connection; and any combination thereof.
 76. The system according to any claim herein, wherein the algorithm is configured to convert information from an imaging coordinate system to a material deposition coordinate system
 77. The system according to claim 76, wherein the imaging coordinate system comprises Cartesian coordinates and wherein the material deposition coordinate system comprises a cylindrical, spherical and/or curvilinear coordinate system.
 78. The system according to any claim herein, wherein the material delivery device comprises at least one nozzle, and wherein the algorithm is configured to create a pathway of motion for the at least one nozzle.
 79. The system according to claim 78, wherein the algorithm creates the pathway of motion based on one or more off limits locations.
 80. The system according to claim 78, wherein the pathway of motion avoids portions of the 3D covering that have already been created.
 81. The system according to claim 78, wherein the pathway of motion avoids the tubular conduit.
 82. The system according to claim 78, wherein the material delivery device comprises a mandrel, and wherein the pathway of motion avoids the mandrel.
 83. The system according to claim 78, wherein the pathway of motion minimizes dissipation of heat to the tubular conduit.
 84. The system according to claim 83, wherein the pathway of motion reduces multiple passes of delivery of material in neighboring regions of the tubular conduit within a time period.
 85. The system according to any claim herein, wherein the algorithm is configured to perform a self-diagnostic.
 86. The system according to claim 85, further comprising at least one sensor configured to produce a signal, wherein the self-diagnostic is based on the signal from the at least one sensor.
 87. The system according to claim 86, wherein the sensor comprises one or more sensors selected from the group consisting of: an optical sensor; a laser; a magnetic sensor; an electrical sensor; an energy sensor; a pressure sensor; a force sensor; a strain gauge; a position sensor; a flow sensor; a sound sensor; an ultrasound sensor; a humidity sensor; and any combination thereof.
 88. The system according to claim 85, wherein the self-diagnostic is configured to assess a parameter selected from the group consisting of: electrical connection status; rotational speed; translational speed; nozzle status; material delivery status; temperature; chamber environment condition; energy delivered; home position; a distance between two components of the system; and any combination thereof.
 89. The system according to any claim herein, wherein the algorithm is configured to create the construction signal based on a property of the tubular conduit.
 90. The system according to claim 89, wherein the construction signal produces a 3D covering that provides mechanical support to the tubular conduit.
 91. The system according to claim 89, wherein the construction signal produces a 3D covering with varied properties along a length of the tubular conduit.
 92. The system according to any claim herein, wherein the material delivery device comprises at least one nozzle.
 93. The system according to claim 92, wherein the material delivery device comprises at least two nozzles.
 94. The system according to any claim herein, wherein the material delivery device comprises a 3D printer.
 95. The system according to any claim herein, wherein the material delivery device is configured to deliver the material using an additive printing process.
 96. The system according to any claim herein, wherein the material delivery device is configured to deliver the material as a series of layers.
 97. The system according to any claim herein, wherein the material delivery device comprises a device selected from the group consisting of: a 3D printer; a layer printing device; an electrospinning device; a melt-spinning device; a melt-electrospinning device; a misting assembly; a sprayer; an electrosprayer; a fused deposition device; a selective laser sintering device; a fiber dispenser; a wire dispenser; a thread dispenser; a resin deposition device, such as a UV-curable resin deposition device; a stereolithography device; a phase separation device; a wet spinning device; a dip coating device; a lathe; a milling machine; a chemical etching device; a plasma etching device; a negative mold-over device; an injection molding device; and any combination thereof.
 98. The system according to claim 97, wherein the material delivery device comprises two or more devices selected from the group consisting of: a 3D printer; a layer printing device; an electrospinning device; a melt-spinning device; a melt-electrospinning device; a misting assembly; a sprayer; an electrosprayer; a fused deposition device; a selective laser sintering device; a fiber dispenser; a wire dispenser; a thread dispenser; a resin deposition device, such as a UV-curable resin deposition device; a stereolithography device; a phase separation device; a wet spinning device; a dip coating device; a lathe; a milling machine; a chemical etching device; a plasma etching device; a negative mold-over device; an injection molding device; and any combination thereof.
 99. The system according to any claim herein, wherein the material comprises one or more materials selected from the group consisting of: synthetic polymer; natural polymer; protein; metal; metal alloy; collagen; elastin; a glycosaminoglycan;a proteoglycan; an alginate; cellulose; gelatin; silk fibroin; fibrinogen; chitosan; an enzyme; fibronectin; glycerin; integrin; keratin; a vitamin; a carbohydrate; a monosaccharide; a disaccharide; a polysaccharide; a nucleoside; abductin; lignin; a glycolipid; a phospholipid; a sterol; shrilk; cobalt-chrome; nitinol; aluminum oxide; magnesium; iron; zinc; steel; titanium; vitalium; alacrite; platinum; gold; silver; copper; manganese; a polyester; a polyurethane; a polycarbonate; a polyether; a polysulfone; a polyamide; a polyetheramide; a polystyrene; a polybutadiene; a polyisoprene; a poly(methyl methacrylate); a polyanhydride; a polydimethylsiloxane; a polydioxanone; polyethylene; glycol; polyethylene terephthalate; a polyglycolide; a polyhydroxyalkanoate; polyimide; polytetrafluoroethylene; polyvinylidene fluoride; polyethylene; polypropylene; polyvinylfluoride; polyvinylchloride; polyacylonitrile; silicone; a ceramic; a bioceramic; a bioglass; a composite material; and any combination thereof.
 100. The system according to any claim herein, wherein the 3D covering comprises varied properties along its length.
 101. The system according to claim 100, wherein the 3D covering comprises at least one customized portion.
 102. The system according to any claim herein, wherein the 3D covering comprises at least a portion with a thickness from about 10 micrometer (μm) to about 1 centimeter (cm).
 103. The system according to claim 102, wherein the 3D covering comprises at least a portion with a thickness from about 50 μm to about 500 μm.
 104. The system according to claim 102, wherein the 3D covering comprises at least a portion with a thickness from about 200 μm to about 300 μm.
 105. The system according to any claim herein, wherein the 3D covering comprises at least a portion with a bulk porosity less than about 99%.
 106. The system according to claim 105, wherein the 3D covering comprises at least a portion with a bulk porosity from about 30% to about 80%.
 107. The system according to claim 105, wherein the 3D covering comprises at least a portion with a bulk porosity from about 50% to about 70%.
 108. The system according to any claim herein, wherein the 3D covering comprises a length from about 1 millimeter (mm) to about 1 meter (m).
 109. The system according to claim 108, wherein the 3D covering comprises a length from about 3 centimeter (cm) to about 50 cm.
 110. The system according to claim 108, wherein the 3D covering comprises a length from about 20 cm to about 30 cm.
 111. The system according to any claim herein, wherein the 3D covering comprises at least a portion with a compliance under a physiologic load that is less than about 99%.
 112. The system according to claim 111, wherein the 3D covering comprises at least a portion with a compliance under a physiologic load that is from about 1% to about 50%.
 113. The system according to claim 111, wherein the 3D covering comprises at least a portion with a compliance under a physiologic load that is from about 10% to about 25%.
 114. The system according to any claim herein, wherein the 3D covering comprises at least a portion with an ultimate strength from about 0.1 Megapascal (MPa) to about 500 MPa.
 115. The system according to claim 114, wherein the 3D covering comprises at least a portion with an ultimate strength from about 0.5 MPa to about 100 MPa.
 116. The system according to claim 114, wherein the 3D covering comprises at least a portion with an ultimate strength from about 1 MPa to about 10 MPa.
 117. The system according to any claim herein, wherein the 3D covering comprises at least a portion with a biodurability from about 1 hour to about 10 years.
 118. The system according to claim 117, wherein the 3D covering comprises at least a portion with a biodurability from about 48 hours to about 2 years.
 119. The system according to claim 117, wherein the 3D covering comprises at least a portion with a biodurability from about 3 months to about 6 months.
 120. The system according to any claim herein, wherein the 3D covering comprises a drug, and wherein the 3D covering is configured to release the drug for a duration from about 1 hour to about 10 years.
 121. The system according to claim 120, wherein the 3D covering is configured to release the drug for a duration from about 48 hours to about 2 years.
 122. The system according to claim 120, wherein the 3D covering is configured to release the drug for a duration from about 3 months to about 6 months.
 123. The system according to any claim herein, wherein the 3D covering comprises at least a portion with a macropore size from about 10 μm to about 1000 μm.
 124. The system according to claim 123, wherein the 3D covering comprises at least a portion with a macropore size from about 20 μm to about 200 μm.
 125. The system according to claim 123, wherein the 3D covering comprises at least a portion with a macropore size from about 50 μm to about 100 μm.
 126. The system according to any claim herein, wherein the 3D covering comprises at least a portion with a macropore spacing from about 10 μm to about 1000 μm.
 127. The system according to claim 126, wherein the 3D covering comprises at least a portion with a macropore spacing from about 100 μm to about 500 μm.
 128. The system according to claim 126, wherein the 3D covering comprises at least a portion with a macropore spacing from about 200 μm to about 400 μm.
 129. The system according to any claim herein, wherein the 3D covering comprises at least a portion with a water permeability of less than about 300 milliliter per centimeter squared per minute (ml/cm²/min).
 130. The system according to claim 129, wherein the 3D covering comprises at least a portion with a water permeability from about 50 ml/cm²/min to about 200 ml/cm²/min.
 131. The system according to claim 129, wherein the 3D covering comprises at least a portion with a water permeability from about 100 ml/cm²/min to about 150 ml/cm²/min.
 132. The system according to any claim herein, wherein the 3D covering comprises a texture with from about 0.25 nanometer (nm) to about 50 μm roughness value Ra.
 133. The system according to claim 132, wherein the 3D covering comprises a texture with from about 0.2 μm to about 12.5 μm roughness value Ra.
 134. The system according to claim 132, wherein the 3D covering comprises a texture with from about 1.6 μm to about 6.3 μm roughness value Ra.
 135. The system according to any claim herein, wherein the 3D covering comprises a suture retention strength up to about 1 kilogram-force (Kgf).
 136. The system according to claim 135, wherein the 3D covering comprises a suture retention strength of from about 50 gram-force (gf) to about 500 gf.
 137. The system according to claim 135, wherein the 3D covering comprises a suture retention strength of from about 100 gf to about 200 gf.
 138. The system according to any claim herein, wherein the 3D covering comprises at least a portion with a kink radius of up to about 1 meter (m).
 139. The system according to claim 138, wherein the 3D covering comprises at least a portion with a kink radius of from about 5 millimeter (mm) to about 100 mm.
 140. The system according to claim 138, wherein the 3D covering comprises at least a portion with a kink radius of from about 10 mm to about 20 mm.
 141. The system according to any claim herein, wherein the 3D covering comprises fibers with a width and/or diameter from about 10 μm to about 1 mm.
 142. The system according to claim 141, wherein the 3D covering comprises fibers with a width and/or diameter from about 20 μm to about 500 μm.
 143. The system according to claim 141, wherein the 3D covering comprises fibers with a width and/or diameter from about 50 μm to about 100 μm.
 144. The system according to any claim herein, wherein at least a portion of the 3D covering comprises a greater axial compliance than radial compliance.
 145. The system according to claim 144, wherein the at least a portion of the 3D covering comprises a majority of fibers that are circumferentially oriented.
 146. The system according to any claim herein, wherein at least a portion of the 3D covering comprises relatively equal axial compliance and radial compliance.
 147. The system according to claim 146, wherein the at least a portion of the 3D covering comprises a majority of fibers that are anisotropically oriented.
 148. The system according to any claim herein, wherein the 3D covering comprises a material selected from the group consisting of: fiber reinforced material; particle reinforced material; flake reinforced material; a multi-layered material; a segmented material; and any combination thereof.
 149. The system according to any claim herein, further comprising a user interface.
 150. The system according to claim 149, wherein the system is configured to display an image of the tubular conduit on the user interface.
 151. The system according to claim 150, wherein the displayed image is a 3D image.
 152. The system according to claim 150, wherein the system is configured to allow a user to modify the displayed image.
 153. The system according to claim 149, wherein the system is configured to display an image of a proposed 3D covering.
 154. The system according to claim 153, wherein the displayed image is a 3D image.
 155. The system according to claim 153, wherein the system is configured to allow a user to modify the displayed image.
 156. The system according to claim 149, wherein the user interface comprises a user control comprising an electronic model modifying tool.
 157. The system according to claim 156, wherein the tool is configured to modify a model of the tubular conduit.
 158. The system according to claim 156, wherein the tool is configured to modify a model of a proposed 3D covering.
 159. The system according to claim 156, wherein the tool comprises a property modifying function selected from the group consisting of: smooth; erase; spline; fillet, fill; insert a building block; and any combination thereof.
 160. The system according to claim 159, wherein the tool comprises a property modifying function including inserting a building block, the building block comprising an electronic model selected from the group consisting of: anastomosis; dimple; reinforcing spline; and any combination thereof.
 161. The system according to claim 149, wherein the tool is configured to measure distance.
 162. The system according to claim 149, wherein the construction signal is based on information provided by a user of the system via the user interface.
 163. The system according to any claim herein, wherein the material delivery device further comprises a modification assembly configured to modify at least one of the 3D covering or the tubular conduit.
 164. The system according to claim 163, wherein the modification assembly is configured to deliver energy to at least one of the 3D covering or the tubular conduit.
 165. The system according to claim 164, wherein the energy comprises heat and/or cooling.
 166. The system according to claim 163, wherein the modification assembly is configured to deliver a second material to at least one of the 3D covering or the tubular conduit.
 167. The system according to claim 166, wherein the second material comprises a material selected from the group consisting of: solvent; drug; agent; and any combination thereof.
 168. The system according to claim 163, wherein the modification assembly is configured to deliver moisture to at least one of the 3D covering or the tubular conduit.
 169. The system according to any claim herein, further comprising a target onto which the material is delivered.
 170. The system according to claim 169, wherein the target comprises a mandrel configured to rotate.
 171. The system according to claim 169, wherein the material delivery device is constructed and arranged to produce the target.
 172. The system according to claim 169, wherein the target comprises a disposable component.
 173. The system according to any claim herein, further comprising a sterile barrier constructed and arranged to maintain sterility between the material delivery device and one or more other portions of the system.
 174. A graft device produced by a system of any claim herein, wherein the graft device comprises: a tubular conduit; a 3D covering surrounding the tubular conduit, wherein the 3D covering is produced by a material delivery device based on image data of the tubular conduit.
 175. The graft device according to any claim herein, wherein the tubular conduit comprises a discrete feature and the 3D covering comprises at least one customized portion positioned relative to the discrete feature.
 176. A method of producing a graft device using the system of any claim herein.
 177. The method according to any claim herein, comprising: (1) producing image data of a tubular conduit; (2) receiving the image data of the tubular conduit and creating an electronic model of the tubular conduit; (3) creating an electronic model of a 3D covering; (4) delivering material to produce a 3D covering.
 178. The method according to claim 177, further comprising modifying the electronic model of the tubular conduit produced in (2).
 179. The method according to claim 177, further comprising modifying the electronic model of the 3D covering produced in (3).
 180. The method according to claim 177, wherein the 3D covering is produced in (4) by delivering the material onto the tubular conduit.
 181. The method according to claim 177, further comprising: (5) placing the 3D covering about the tubular conduit.
 182. The system according to claim 99, wherein the material comprises the glycosaminoglycan, and wherein the glycosaminoglycan comprises heparin, heparan sulfate, chondroitin sulfate, dermatan sulfate, keratan sulfate, and/or hyaluronic acid, or any combination thereof.
 183. The system according to claim 99, wherein the material comprises the proteoglycan, and wherein the proteoglycan comprises decorin, biglycan, testican, bikunin, fibromodulin, lumican, versican, perlecan, neurocan, aggrecan and/or brevican. 